ViewPoints Interview: Vigeo Therapeutics’ Dr. Lou Vaickus and Dr. Jing Watnick Share Insights on VT1021 Data Presented at SITC 2020

In a recent interview with PharmaShots, Dr. Jing Watnick, Co-Founder and Chief Executive Officer, and Dr. Lou Vaickus, Interim Chief Medical Officer at Vigeo shared their views on the data findings presented at the SITC 2020 Annual Meeting that demonstrated VT1021 as a single-agent has a favorable safety profile and shows early signals of clinical activity across a wide variety of solid tumors, including pancreatic cancer and glioblastoma.

Shots:

  • VT1021 is a first-in-class, dual-modulating therapy that blocks the CD47 immune checkpoint and activates CD36, stimulating cytotoxic T-cell functions, inducing apoptosis in tumor and endothelial cells, and increasing the phagocytosis of the tumor by M1 macrophages by stimulating the production of Tsp-1
  • The compound initially targets pancreatic cancer, glioblastoma multiforme (GBM) and ovarian cancer
  • Vigeo Therapeutics is open for collaborations to advance its clinical program and build pipeline

Tuba:  Can we have a glimpse of the poster presented at the Society for Immunotherapy of Cancer’s (SITC) 2020 Annual Meeting?

Tuba:  Highlight the key points of the VT1021 development program and its mechanism of action. 

Lou: VT1021 is a first-in-class, dual-modulating compound that blocks the CD47 immune checkpoint and activates CD36, stimulating cytotoxic T-cell functions, inducing apoptosis in tumor and endothelial cells, and increasing the phagocytosis of the tumor by M1 macrophages by stimulating the production of thrombospondin-1 (Tsp-1). Vigeo is developing VT1021 as a therapeutic agent across a range of cancers, with a current focus on solid tumors.

Source: Vigeo

Tuba:  Describe in brief about the specific disease targets of VT1021. 

Lou: Currently the target indications for VT1021 are pancreatic cancer, glioblastoma multiforme (GBM) and ovarian cancer.  Vigeo is also targeting patients with tumors that express high levels of both CD47 and CD36 as a biomarker based/indication agnostic strategy.

Tuba:  Discuss the key findings from the interim clinical data from the P-I/II study of VT1021. 

Lou: Dual modulation of CD47 and CD36 promotes complementary anti-tumor activity as 75% of patients who achieved a PR or SD had high expression of both CD47 and CD36 prior to entering the study.

Tuba:  When can we expect the complete results of the P-I/II study and initiation of P-II study?

Lou: Escalation has been completed and expansion is expected to be completed by 2Q of 2021. We expect to initiate combination studies in 2Q of 2021.

Tuba:  What are the unique attributes about Vigeo’s lead candidate VT1021? 

Lou: Vigeo’s lead asset, VT1021, is a first-in-class dual modulating compound that blocks the CD47 immune checkpoint and activates CD36, which induces apoptosis and increases the M1:M2 macrophage ratio.  VT1021 achieves this through stimulation of thrombospondin-1 (Tsp-1).  The goal of these dual-modulating effects is conversion of immuno-suppressive, or “cold,” tumors that don’t respond to immuno-oncology agents, to immuno-stimulated, or “hot,” tumors that are potentially more receptive to immuno-oncology agents. Vigeo is developing VT1021 as a therapeutic agent across a range of cancers, with a current focus on solid tumors. Pre-clinical results have demonstrated that single-agent VT1021 causes tumor regression at both the primary and metastatic sites.

Tuba:  What were the major highlights about the dose escalation portion of first in human trial with VT1021? 

Lou: The dose escalation study was marked by a very clean safety profile, an expected and dose dependent pharmacokinetic profile, and the attainment of changes in desired biomarkers in patients that were predicted in nonhuman animal models.  As such the recommended Phase 2 dose was determined based on a combination of safety, pharmacokinetic, and pharmacodynamic parameters.  Additionally, there was a very overall high disease control rate (SD+PR) of 43% (12/28). When analyzing patients with high levels of both CD36 and CD47, the disease control rate increased to 80% (8/10).  

Tuba:  How do you feel about the development status of VT1021 so far?

Lou: We are very encouraged by the development of the biomarker-based strategy and feel that this will significantly impact the clinical development of VT1021.  Early results in the indication expansion cohorts are promising and we are cautiously optimistic. In addition, the clean safety profile allows for combinability with other immunomodulatory and chemotherapy drugs.

Tuba:  What are the other programs that we can expect to escalate further from Vigeo’s pipeline? 

Lou: There are several preclinical-stage programs in the pipeline focusing on TME modulation.

Tuba:  Do you plan for any partnerships for the commercialization strategies of VT1021? 

Lou: We are continuously evaluating potential partnerships and remain open to any number of possibilities as we work to advance our clinical program and build out our pipeline. 

About Authors:

Dr. Jing Watnick is a co-founder of Vigeo and leads the company as its CEO. She has over 20 years of experience in the pharmaceutical industry, including roles in program and portfolio management, strategic planning, business development, alliance management, and preclinical and clinical research.

Lou Vaickus serves as Interim CMO of Vigeo. He has over 30 years of experience that began as an academic scientist, then practicing physician, then spanned into the industry with preclinical, clinical, and globally marketed pharmaceutical products.

Related Post: ViewPoints Interview: Janssen’s Kiran Patel Shares Insights on Amivantamab for Metastatic EGFR Exon 20+ NSCLC

The post ViewPoints Interview: Vigeo Therapeutics’ Dr. Lou Vaickus and Dr. Jing Watnick Share Insights on VT1021 Data Presented at SITC 2020 first appeared on PharmaShots.

ViewPoints Interview: Janssen’s Kiran Patel Shares Insights on Amivantamab for Metastatic EGFR Exon 20+ NSCLC

In a recent interview with PharmaShots, Kiran Patel, Vice President Clinical Development, Solid Tumor Franchise at Janssen shared his views on the regulatory submission of Amivantamab for the Treatment of Patients with Metastatic Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations.

Shots:

  • Janssen reported the BLA submission to the US FDA seeking approval of Amivantamab for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations
  • The filing is the first regulatory submission for patients with exon 20 insertion mutations and it also marks Janssen’s first filing for the treatment of patients with lung cancer
  • Amivantamab is an investigational bispecific antibody that targets both a driver mutation as well as a resistance mechanism and has received BTD in March, is being studied as a monothx. & combination therapy in NSCLC with EGFR mutations, including in earlier lines of therapy

Tuba: A quick highlight of clinical data submitted for the BLA submission of Amivantamab to the US FDA?

Kiran: On December 3, 2020, Janssen submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA)  seeking approval of amivantamab for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.

The BLA is supported by data from the monotherapy arm of the Phase 1 CHRYSALIS study, a multi-center, open-label, multi-cohort study. The study evaluated the safety and efficacy of amivantamab as a monotherapy and in combination with lazertinib, a novel third-generation EGFR tyrosine kinase inhibitor (TKI), in adult patients with advanced NSCLC.

The submission of this BLA is an important step as we hope to advance a new therapeutic option for patients with NSCLC and exon 20 insertion mutations for whom there are currently no approved targeted therapies. The current standard of care for EGFR Exon 20 insertion mutation-positive NSCLC is chemotherapy.

Tuba: What is the mechanism of action of Amivantamab and how does it work?

Kiran: Amivantamab is an investigational, fully-human, EGFR, and mesenchymal-epithelial transition factor (MET) bispecific duo-body with immune-cell directing activity that targets tumors with activating and resistance EGFR and MET mutations and amplifications. As a monotherapy, amivantamab has shown activity in patients with diverse EGFR mutant disease.

Tuba: Why is Janssen focused on metastatic NSCLC with EGFR exon 20 insertion mutations?

Kiran: Lung cancer is the leading cause of cancer deaths worldwide. In the U.S., lung cancer is the second most common cancer in both men and women, after skin cancer and NSCLC makes up 80 to 85 percent of all lung cancers. EGFR genetic alterations are among the most common driver mutations for NSCLC and are present in 10 to 15 percent of patients with NSCLC. Additionally, EGFR exon 20 insertion mutations identify a distinct subset of lung adenocarcinomas, accounting for at least nine percent of all EGFR mutations.

Currently, there are currently no FDA-approved targeted therapies for patients with NSCLC who have EGFR exon 20 insertion mutations. Given this significant unmet need, we are committed to improving outcomes for patients diagnosed with this complex, deadly disease. Janssen is committed to advancing targeted therapies for patients living with genetically defined lung cancer where there remains a high unmet need for new treatment options.

Tuba: When can we expect approval and launch of amivantamab in the US?

Kiran: The BLA submission was completed on December 3, 2020. In March 2020, amivantamab received FDA Breakthrough Therapy Designation, which is granted to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition. We do not speculate on potential approval timelines.

Tuba: When can we expect results from the CHRYSALIS combination arm?

Kiran: We presented interim data from the CHRYSALIS combination arm at the ESMO 2020 Virtual Congress in September. Data showed the combination of amivantamab and lazertinib achieved a 100 percent overall response rate in the cohort of patients with treatment-naïve EGFR-mutated NSCLC. We look forward to the continued evaluation of amivantamab in combination with lazertinib in EGFR mutation-positive NSCLC patients.

Tuba: How many patients have been part of the expanded access program (EAP) in the US?

Kiran: Jansen established an expanded access program (EAP) for EGFR Exon 20 insertion patients in the U.S. who may be eligible to obtain access to amivantamab during review of the BLA. For information about Janssen’s pre-approval access program, visit https://www.janssen.com/compassionate-use-pre-approval-access. We cannot disclose patient enrollment numbers for the EAP.

Tuba: Has Janssen started any HCP awareness, HCP education, and patient support and awareness programs?

Kiran: We recently launched a website, Hidden EGFR Threats, intended to inform physicians and patients about the multiple threats of EGFR-mutated advanced NSCLC.

Tuba: Is Janssen planning to assess amivantamab in other indications?

Kiran: The results from the CHRYSALIS study have led to new studies to further evaluate the potential of amivantamab and lazertinib combination therapy. The Phase 3 MARIPOSA study will compare amivantamab in combination with lazertinib with osimertinib in untreated advanced EGFR-mutated NSCLC, and a Phase 2 trial, CHRYSALIS-2 is ongoing and enrolling patients who have progressed after treatment with osimertinib and chemotherapy.

Tuba: Any near-future plans to file for EU or any other geographies?

Kiran: We have plans to pursue approval of amivantamab in other markets with the goal of bringing this novel therapy to patients around the world who may benefit, but it is premature to speculate about timing.

Image Source: Medical Forum

About Author:

Kiran Patel is a Vice President of Clinical Development, Solid Tumor Franchise at Janssen and is serving Janssen since 2015.

Related Post: ViewPoints Interview: Janssen’s Andrew Greenspan Shares Insights on the Data Presented at ACR2020

The post ViewPoints Interview: Janssen’s Kiran Patel Shares Insights on Amivantamab for Metastatic EGFR Exon 20+ NSCLC first appeared on PharmaShots.

ViewPoints Interview: Janssen’s Andrew Greenspan Shares Insights on the Data Presented at ACR2020

In a recent interview with PharmaShots, Andrew Greenspan, MD, VP Medical Affairs of Janssen Immunology shared his views on Janssen’s commitment to advance research in rheumatic disease.

Shots:

  • Janssen presented clinical trial results in 35 abstracts featuring findings across PsA, RA, and SLE at ACR Convergence 2020 Virtual Scientific Program
  • Sixteen abstracts focus on Tremfya in adults with active PsA, including 52-week safety and efficacy data, axial disease-related endpoints, and more.
  • Other presentations feature new research across Janssen’s portfolio of medications including Simponi Aria (golimumab), Stelara (ustekinumab), and Remicade (infliximab)

Tuba: How was your virtual experience at ACR2020? Can we have an insight on data presented at ACR 2020?

Andrew: Speaking on behalf of those who represented Janssen at the conference – we are so proud of the breadth of data presented at ACR this year. Even though the conference looked a little different than it has in years past, we were still thrilled to share our findings – including 35 abstracts highlighting our research across psoriatic arthritis, rheumatoid arthritis and system lupus erythematosus. Specifically, we presented 16 abstracts focused on TREMFYA in adults with active psoriatic arthritis, including 52-week safety and efficacy data, spinal disease-related endpoints, as well as analyses that highlight patient-reported outcome measures including fatigue. Other presentations featured new research across our portfolio of medications.

Tuba: As the focus of the presentation is Tremfya, give a quick review about the clinical data supporting the therapy?

Janssen’s Tremfya (guselkumab) Receives the US FDA's Approval as the First Selective IL-23 Inhibitor for Active Psoriatic Arthritis
Source: MPR

Andrew: As a company, we’re constantly striving to keep our foot on the gas to create new clinical evidence and innovation. As a testament to this, we were proud to expand our rheumatology portfolio this year with the U.S. FDA approval of TREMFYA for adult patients with active psoriatic arthritis, which was first approved to treat adults with plaque psoriasis in 2017. Let me share some additional information on the compelling data we shared at ACR:

  • Data from two Phase 3 clinical trials, DISCOVER-1 and DISCOVER-2, showed that TREMFYA improved fatigue in adult patients with active psoriatic arthritis and maintained response through 52 weeks of active treatment, as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale. TREMFYA is the first and only treatment approved for active psoriatic arthritis to have an improvement in fatigue as measured by FACIT-F in the product label.
  • The positive outcomes in fatigue assessment add to the body of data for TREMFYA, which has shown improvements in multiple clinical outcomes including joint symptoms, skin symptoms, soft tissue inflammation, and physical function.
  • Fatigue is considered one of the three most important symptoms by patients with active psoriatic arthritis, and moderate to severe fatigue occurs in up to 50 percent of these patients.

Tuba: Can we have a glance at Janssen’s immunology portfolio as it is working in immunology over the past two decades?

Source: Janssen

Andrew: At Janssen, we have an unmatched track record of translating science into effective therapeutics. In the past two decades, my colleagues at Janssen have developed five advanced treatments for 31 indications resulting in the treatment of more than 5 million patients living with autoimmune disease. Treatments in our immunology portfolio treat a variety of conditions for various patient populations, such as plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, polyarticular juvenile idiopathic arthritis, rheumatoid arthritis, ulcerative colitis and Crohn’s disease. These treatments include TREMFYA (guselkumab), SIMPONIARIA (golimumab), STELARA (ustekinumab), SIMPONI (guselkumab) and REMICADE (infliximab). Looking ahead to potential future treatments, we have a robust pipeline, with 21 first-in-class Phase 2 or 3 trials underway. We’re eager to explore treatment options for less common diseases like hidradenitis suppurativa and Sjogren’s syndrome, where there are fewer or no advanced treatment options currently available.

Tuba: What are Janssens’s efforts in developing biomarkers and co-diagnostics to personalize medicine in the field of rheumatic diseases?

Andrew: We are exploring the development of tools that will better allow us to measure disease activity in patients, including sensors (digital health, actigraphy), novel biomarkers, new endpoints and new patient-reported outcomes to better identify patients appropriate for our medicines and to evaluate the efficacy and safety of them.

 Tuba:  Apart from Tremfya, Simponi, Simponi Aria, and Stelara, what next can we expect from Janssen to transform the lives of patients with autoimmune diseases? What will be your next move (in terms of the combination of internal research and development, external collaborations, and industry consortia) to complement Janssen’s existing portfolio of immunology? Who are Janssen’s potential competitors in the field of autoimmune diseases?

Andrew: I’m very proud of where our research in immunology stands and where it is leading us. While treatments today have made a big difference in the lives of many patients, there certainly remains a significant need for medicines that work better, faster, and longer. Instead of focusing on the competition, we prefer to focus on unmet needs. By unlocking new pathways, mechanisms, and regimens in our treatment options, we strive to provide innovative treatment options to patients. Looking further ahead at our mid-to-late stage pipeline, we have 21 first-in-class Phase 2 or 3 trials underway and we’re eager to explore treatment options for less common diseases like hidradenitis suppurativa and Sjogren’s syndrome, where there are fewer or no advanced treatment options currently available.

Tuba: Can we have a glimpse of Janssen’s work in other therapeutics areas? Can you list out some key advancements for our readers?

Andrew: In addition to immunology, we focus on areas of medicine where we can make the most impact, including Cardiovascular & Metabolism, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension, where we have delivered 18 new medicines in less than nine years. For more information about these specific therapeutic areas, I would be happy to put you in touch with a specialist on our team to learn more about the innovative work being done in these fields.

Tuba: Does the global pandemic affect Janssen’s ongoing as well as future clinical trials?

Andrew: As the world continues to navigate the new normal brought on by COVID-19, there has been an undeniable effort to ensure continuity of care and advance research by a wide range of experts, from healthcare professionals and clinical trial site teams to research partners and regulatory bodies. We at Janssen recognize and remain committed to supporting everyone involved in clinical research. To learn more about Janssen’s commitment to clinical trial research, visit: https://www.janssen.com/clinical-trials/janssen-global-development-leadership-commitment-clinical-research.

Image Source: MIMS Malaysia

About Author:

Andrew Greenspan, MD is a vice president of Immunology Medical Affairs at Janssen and has joined J&J in 2003.

Related Post: ViewPoints Interview: GSK’s Dr. Riju Ray Shares Insights on the Role of Community-Based Pulmonologists in Improving COPD Management Among PCPs

The post ViewPoints Interview: Janssen’s Andrew Greenspan Shares Insights on the Data Presented at ACR2020 first appeared on PharmaShots.

ViewPoints Interview: GSK’s Dr. Riju Ray Shares Insights on the Role of Community-Based Pulmonologists in Improving COPD Management Among PCPs

In a recent interview with PharmaShots, Dr. Riju Ray, MD, PhD, Senior Medical Lead at GSK, leading US medical affairs across asthma and COPD shared his views on how community-based pulmonologists are improving COPD management and education among referring PCPs.

Shots:

  • Pulmonologists identified 12 strong to moderate predictors of future COPD exacerbations, some of which were evaluated less frequently. COPD is frequently underdiagnosed, and this may be partially due to a lack of adequate knowledge and testing at the primary care level, highlighting the need for further education improve patient care
  • When evaluating COPD traits, pulmonologists were most likely to evaluate behavioral traits, exacerbation history and recovery time rather than traits that require testing, as acknowledged by the standard of care (GOLD guidelines). Failure to evaluate testing-based traits creates an overdependence on physician-patient communication, which is already a recognized key challenge
  • Community-based pulmonologists play an important role in the management of COPD, and the majority of respondents were also in a position to influence COPD management practices of colleagues. However, the opportunity to educate primary care physicians on COPD management and exacerbation prevention was not utilized by the majority of survey respondents, suggesting a need to more strongly engage specialists in education efforts

Tuba: Please discuss the epidemiology of the chronic obstructive pulmonary disease (COPD)?

Riju: COPD, or chronic obstructive pulmonary disease, is a progressive lung disease. There are more than 16.4 million people in the U.S. that are diagnosed with COPD, and it is one of the leading causes of death worldwide. While there is no cure for COPD, it is treatable, and with daily management, those with the disease can maintain good quality of life.

Tuba: Can we have a key point of the whitepaper published in Chest Clinical Perspectives in a non-scientific way?

Riju: In the recent study funded by GSK and co-developed by CHEST and GSK, we assessed the approaches pulmonary specialists take when they think of managing COPD exacerbations (or flare-ups) and what clinical perspectives come to mind when they consider future risk of these COPD exacerbations for their patients. These COPD exacerbations, or COPD flare-ups, speed up lung function decline and often lead to hospitalizations, which impact the health and quality of life for people with COPD. Research shows that frequent exacerbations that require hospitalization are also associated with higher mortality. Hospitalizations also lead to greater impact on daily life, decreased ability to work and increased burden on family caregivers, so it is important to help people with COPD reduce their chances of experiencing a COPD exacerbation.

Source: Biophysical Society

Tuba: What were the objectives of the research conducted by CHEST?

Riju: The objectives of the survey were to:

  • Assess the frequency with which pulmonary, extrapulmonary, and behavioral traits of COPD patients are evaluated in pulmonology practices.
  • Assess which disease characteristics pulmonologists use to predict the occurrence and severity of exacerbations in patients with COPD, including those who have no history of exacerbations.
  • Identify barriers to assessing these disease characteristics in pulmonology practices.
  • Assess how often pulmonologists are actively involved sharing their knowledge of COPD treatment and management with their referring primary care physicians.

Tuba: Discuss the role of pulmonologists in improving the management of COPD.

Riju: Pulmonologists work with patients to develop a proper COPD management plan and participate in the development of treatment plans. Pulmonologists are also in a position to better educate their referral primary care physicians. According to the survey, COPD is frequently underdiagnosed, which may be partially due to primary care physicians’ (PCPs) lacking knowledge on the disease. It’s important for pulmonologists to utilize their position to educate PCPs on how to administer tests, and interpret results, and plan tailored disease management plans for their patients with COPD.

Tuba:  What were the findings of the research conducted by CHEST/GSK?

Riju: The survey uncovered a few key insights on COPD exacerbation predictors and the role of pulmonologists in better managing future COPD exacerbation risk:

  • There are 12 strong disease characteristics that pulmonologists determined to be predictors of a COPD exacerbation.
  • Pulmonologists are more likely to evaluate behavioral traits that do not require testing than pulmonary and extrapulmonary factors.
  • Most (71%) of pulmonologists surveyed use a strategy-based approach like the GOLD while 29% said their management approach is dependent on a patient’s symptoms.
  • The opportunity to educate other physicians on COPD management and exacerbation prevention is not utilized.In fact, only 16% of respondents said they make a routine practice of proactively engaging or informally educating referring physicians on how to evaluate and manage COPD.

Tuba: Can you showcase the GOLD guidelines used by the pulmonologist?

Riju: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy document is used broadly by physicians to guide COPD treatment plans. It categorizes patients according to their level of airflow limitation, symptoms, and comorbidities, and disease stages. However, patients symptom burden and exacerbation history are recommended as 2 key guiding principles for determining optimal treatment. Patients grouped in the same stage of the disease often have variation in symptoms, exacerbations, and risk of mortality, so understanding how to identify and test those characteristics is important to developing a personalized treatment plan.

Tuba: What were the different traits evaluated by the pulmonologist during the research?

Riju: In the survey, pulmonologists evaluated various behavioral, pulmonary and extrapulmonary traits and determined 12 strong COPD exacerbation predictors. The behavioral characteristics include treatment adherence, tobacco use, exacerbation history (especially exacerbations leading to hospitalizations), which do not require testing. Pulmonary and extrapulmonary factors include frailty or airflow limitation, which are evaluated less frequently. This study emphasizes the importance of pulmonologists’ recognition of disease characteristics, laboratory testing, in-office assessments and physician education when developing treatment plans. 

  • When testing-based characteristics are not routinely evaluated as indicated by surveyed pulmonologists, it creates an overdependence on physician-patient communication. While this study did not specifically address communication, we know that both patients and physicians think there is room for improvement in terms of physician-patient communication during medical appointments. It is an extremely important component of the patient-physician relationship and should be considered in any disease management plan.

Tuba: What are the different predictors of future COPD exacerbations? What you consider is the best predictor for exacerbation?

Riju: The best predictor for an exacerbation is exacerbation(s) history; however, it is important for pulmonologists to evaluate other disease characteristics, especially in the absence of exacerbation history. A focus on behavioral elements like smoking cessation and adhering to their treatments especially controller medicines also ranked high from the surveyed pulmonologists. Regardless of exacerbation history, recent studies suggest triple therapy with an ICS, LAMA, and LABA showed the greatest benefit for improving both lung function and preventing exacerbations.

Tuba: What are the educational benefits of using an approach to COPD management?

Riju: As mentioned, COPD is frequently under-diagnosed, so it is important for pulmonologists to utilize all tools available to them between in-office testing, reference of GOLD and evaluation of a patient’s health history when treating people with COPD symptoms. It’s also critical pulmonologists engage PCPs in formal or informal education activities to improve patient care from the front line.

Tuba: Why do you think COPD management is necessary to improve the condition of patients?

Riju: Like any disease, proper disease management is essential to ensuring patients receive optimal care and lead a high quality of life as possible. COPD can worsen over time, especially for people who experience frequent exacerbations, but patients don’t have to settle for a life of breathlessness. Better days are possible for people living with COPD through consistent and comprehensive disease management.

Image Source: Dimerix Limited

About Author:

Dr. Riju Ray is an MD, PhD senior medical lead within the Respiratory team at GSK US medical affairs leading teams across both Asthma and COPD. He is based out of Research Triangle Park in North Carolina.

Related Post: ViewPoints Interview: Genentech’s Ted Omachi Shares Insight on the US FDA’s Approval of Xolair in Nasal polyps

The post ViewPoints Interview: GSK’s Dr. Riju Ray Shares Insights on the Role of Community-Based Pulmonologists in Improving COPD Management Among PCPs first appeared on PharmaShots.

ViewPoints Interview: Genentech’s Ted Omachi Shares Insight on the US FDA’s Approval of Xolair in Nasal polyps

In a recent interview with PharmaShots, Ted Omachi, Global Development Leader for Xolair, and Senior Medical Director of Product Development for Immunology, Genentech shared his views on the approval of Xolair in the US.

Shots:

  • The approval is based on P-III POLYP 1 & 2 trials assessing Xolair vs PBO in 138 & 127 adult patients with nasal polyps who had an inadequate response to nasal corticosteroids respectively
  • Results: @24wks. improvement in NPS (-1.1 vs 0.1 & -0.9 vs -0.3); improvement in NCS (-0.9 vs -0.4 & -0.7 vs -0.2); no new or unexpected safety signals were identified respectively
  • Xolair is the first biologic for the treatment of nasal polyps that targets and blocks IgE. In the US, Novartis & Genentech work together to develop and co-promote Xolair

Tuba: Can you please shed some light on Nasal Polyps? (causes, symptoms, epidemiology, etc.)

Ted: Approximately 13 million people in the U.S. are impacted by nasal polyps, a commonly occurring condition in adults that may be refractory to treatments such as nasal corticosteroids and even surgery. Nasal polyps present as noncancerous growths on the lining of the nasal sinuses or nasal cavity associated with irritation and inflammation and, as such, they can block normal airflow. Nasal polyps may also co-occur with other respiratory conditions, such as allergies and asthma. They may become quite large and develop in both nostrils, leading to a loss of smell, nasal congestion, chronic runny nose, and post-nasal drip. This condition can cause significant long-term symptoms and impact on patients’ lives. While the pathophysiology of nasal polyps is not entirely elucidated, we know that it is an inflammatory condition in which immunoglobulin E (IgE) plays an important role.

Tuba:  A quick highlight of clinical data submitted for the approval of Xolair in nasal polyps to the U.S. FDA.

Ted: The FDA’s approval is based on results from the Phase III POLYP 1 and POLYP 2 pivotal trials conducted in adult patients. To be enrolled in the study, patients needed to have large polyps in both nostrils and significant symptoms, with persistent symptoms and large polyps even after treatment with nasal steroids. Patients were then given either Xolair or placebo, in a blinded fashion, while continuing to receive nasal steroids. Patients who received Xolair had statistically significantly greater improvements, as compared to placebo, over the approximate six-month duration of the study, from baseline to Week 24, in both of the co-primary endpoints: Nasal Polyp Score (NPS) and Nasal Congestion Score (NCS). NPS is an objective measure of the size of the polyps, as determined by endoscopy, while NCS is a measure of the degree of nasal blockage, as determined by patients’ assessment of their own symptoms. The greater improvements in NPS and NCS in the Xolair group as compared to the placebo group were observed as early as the first assessment at Week 4 in both studies. They also had statistically significant improvements in smell, post-nasal drip, and runny nose. The safety profile in POLYP 1 and POLYP 2 was consistent with the established safety profile for Xolair, which is based on more than 17 years of real-world experience in allergic asthma and more than 1.3 million patient-years of usage in clinical practice. 

Tuba: Can you explain how Xolair works for nasal polyps (mechanism of action)?

Ted: Xolair is the first biologic for the treatment of nasal polyps that targets and blocks immunoglobulin E (IgE), a key driver of inflammation. By reducing free IgE, down-regulating high-affinity IgE receptors and limiting mast cell degranulation, Xolair minimizes the release of mediators throughout the allergic inflammatory cascade.

Tuba: Can you provide some insights on RoA for Xolair in Nasal Polyps?

Ted: We do not comment on sales forecasts or projections.

Tuba:  Can our readers have more details on any ongoing and upcoming patients support programs and efforts for patient adherence?

Ted: As a physician, I know firsthand that adherence and access to medicines are some of the most important factors to ensure the safety and effectiveness of treatment for patients. At Genentech, we are committed to helping patients access to the medicines prescribed by their physician, even if they can’t afford them. For more than 20 years, we have helped more than 2.2 million people get the medicine they need through patient assistance programs like Genentech Access Solutions and the Genentech Patient Foundation.

Tuba: Xolair is now approved in multiple indications including allergic asthma, CIU and nasal polyps. What’s next?

Ted: We are committed to exploring the full potential of Xolair across a range of respiratory diseases.

In August 2020, the FDA accepted our sBLA for a new self-injection option for Xolair prefilled syringe formulation across all approved US indications, with a decision on approval anticipated in Q1 2021.

Additionally, in 2018 the FDA granted Breakthrough Therapy Designation to Xolair as a potential treatment for food allergies. Xolair is currently being investigated as a potential treatment for multiple food allergies in Phase III clinical trial, Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen Oral Immunotherapy in Food Allergic Children and Adults, or OUtMATCH trial. The trial is supported by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, Genentech, and Novartis. We are hopeful about the potential to address this area of the significant need for patients as there are limited FDA-approved treatments that help prevent severe reactions due to food allergies.

Tuba: Are you focusing on approvals in different countries?

Ted: Xolair is approved for nasal polyps-related conditions in several countries outside of the U.S. In August 2020, the European Commission approved Xolair as add-on therapy with intranasal corticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps (CRSwNP) for whom therapy with intranasal corticosteroids does not provide adequate disease control. Additionally, Xolair is approved in more than 10 other countries throughout the world for nasal polyps or CRSwNP. Further regulatory reviews of Xolair to treat patients with CRSwNP (often referred to as nasal polyposis) are currently underway in multiple countries.

Tuba: What kind of pricing difference shall be expected for Xolair for Nasal Polyps vs. Xolair for other indications?

Ted: When determining the prices of our medicines, we take into consideration a number of factors including clinical benefit, patient access, investments required for future medications, and our responsibility to patients, society, and shareholders. The dosing of Xolair for nasal polyps and allergic asthma depends on the patient’s weight and serum IgE levels, which affects the cost of therapy.

About Ted Omachi:

Ted Omachi is a Medical Director in the Product Development Immunology group at Genentech, focusing on late-stage development in respiratory and allergic diseases. He joined Genentech in 2013, starting in the Medical Affairs group before transitioning to Product Development in 2015.

Related Post:  ViewPoints Interview: Genentech’s Ted Omachi Shares Insights on Xolair (omalizumab) PFS

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ViewPoints Article: 3D Bioprinting Represents a Huge Leap in the Pharmaceutical Industry

Three-dimensional technology has been an integral part of the pharmaceutical industry for many years. The medical fraternity has witnessed the clinical benefits of 3D technology such as printed anatomical prostheses, heart valves, biological tissues, hearing aids, and much more. The global 3D printed drugs market was valued at US$ 29 million in 2019 and is expected to grow at a CAGR of 9.1% from 2020 to 2027. The factors driving the 3D printed drugs market growth include the increased delivery of personalized medicines, extensive research, and development activities. Its application in the manufacturing of drugs is very attractive since it caters to personalized medicine. With extensive research and progress in cell biology, nanotechnology, and material sciences, a new concept has surfaced, 3D Bioprinting.

What is 3D Bioprinting?

3D bioprinting, a novel technology, is basically a manufacturing process to generate tissue-like structures that behave as natural tissues. The simplest bio-printed tissue is a single layer, like skin. The ingredients are “biomaterials” i.e. cells and growth factors. A key difference between 3D printing and 3D bioprinting is that a living cell suspension is used in the case of bioprinting rather than thermoplastic, used in the conventional 3D printing method. The cells are usually extracted from the patient or if not possible, adult stem cells are used which are then cultured carefully and converted to “bio-ink” which by its name, prints the desired tissue or organ.

How is 3D Bioprinting done?

  1. 3D Imaging: A standard imaging (CT or MRI scan) is done to get the exact dimensions of the tissue/organ.
  2. 3D Modeling: A mode / blueprint of the organ/tissue is created by using AutoCAD software to avoid the transfer of defects.
  3. Bioink Preparation: it is the combination of the patient`s living cells, compatible basin (gelatin, collagen, etc.) and cell growth factors based.
  4. Printing: Deposition of the prepared bioink Layer-by-layer on the AutoCAD design.
  5. Solidification: Solidifying the structure may be aided by using specific chemicals, UV light, or heat.

Why 3D Bioprint?

The main objective of bioprinting would be to provide an alternative to autologous and allogeneic tissue implants. In the coming time, it will gradually replace animal testing and thereby speed-up the drug development process. The long term objective is to deliver personalized tissues/organ made from the patient`s own cells. It would hypothetically have fewer rejection rates. Who would be the owner of that organ? This could be an ethical challenge to ponder upon.

A small, yet powerful step would be the creation of tissue components for the heart, liver, pancreas, and other vital organs.  In the future, 3D bioprinting will make organs widely available to those who need them, instead of being on a transplant list for many years.

Advantages

  1. Reduce research and development costs by replacing animal testing.
  2. Testing a drug`s efficacy on a fully bioprinted organ/tissue before invitro or human study.
  3. It could solve the current organ transplant waiting list problem.
  4. Customized training materials could be deployed in medical colleges to help train students and physicians.
  5. Accurate cell distribution
  6. High-resolution cell deposition
  7. Scalability

Challenges

  1. There is limited availability of good quality data. This could be due to a lack of interest by the pharmaceutical development researchers, high costs incurred upon the company, and less information on bioinks.
  2. Strict regulations
  3. Cost-estimation is difficult
  4. Reimbursements
  5. Tissue-specific bioink
  6. Improve current 3D Bioprinters to enhance resolution and detailing
  7. Large scale production

The future of 3D bioprinting is bright for the pharmaceutical industry due to the trend of more personalized medical treatments. The increasing demand for customized therapeutics will help the 3D bioprinting industry is emerging. It would become possible to 3D print tissues and even organs, which would make a lot of lives happier and healthier. In the coming years, 3D bioprinting could even help repair a damaged liver. A bioprinted liver patch created from the patient`s own liver cells could be the solution. Finally, 3D bioprinting represents a huge leap forward from animal testing and cell culture.

It is time for India’s nascent 3D bioprinting industry to step up

References:

  1. Samiei N. Recent trends on applications of 3D printing technology on the design and manufacture of pharmaceutical oral formulation: a mini review. Beni-Suef University Journal of Basic and Applied Sciences. 2020 Dec;9:1-2.
  2. Murphy SV, Atala A. 3D bioprinting of tissues and organs. Nature biotechnology. 2014 Aug;32(8):773-85.
  3. Worldwide Industry for 3D Printed Drugs to 2027 – Rising Awareness About 3D Printing Technology Presents Opportunities
  4. 3D Printing & Bioprinting in Pharmaceutical Manufacturing

Image Source: NCBI-NIH

About Co-Author:

Dr. Sunaina Anand, Pharm. D is a Clinical Pharmacist. She currently serves as Medical Affairs Executive in IntelliMed Healthcare Solutions. She previously interned in Tata Memorial Hospital and Columbia Asia Hospital, Bengaluru.

Related Post: ViewPoints Article: Digital Biomarkers

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ViewPoints Interview: ViiV Healthcare’s Kimberly Smith Shares Insight on Data of Long-Acting Cabotegravir and Rilpivirine Presented at IDWeek 2020

In a recent interview with PharmaShots, Kimberly Smith, MD, MPH, Head of Research & Development at ViiV Healthcare shared information on the positive findings presented at the 2020 Infectious Diseases Society of America (IDWeek) and the impact of COVID-19 on the development of long-acting cabotegravir and rilpivirine.

Shots:

  • The company reported the positive findings of a pooled analysis of six ongoing clinical studies which includes P-IIb/IIIb LATTE-2, ATLAS, ATLAS-2M, FLAIR, POLAR, and CUSTOMIZE studies evaluating long-acting cabotegravir and rilpivirine regimen in 1,744 patients with HIV-1 infection across 16 countries
  • The positive findings showed 93% of participants maintained their injection visits amid the COVID-19 with no instances of virologic failure or development of resistance and showed good tolerability
  • Long-acting regimen of cabotegravir and rilpivirine is indicated as a complete regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in patients who are virologically stable and suppressed (HIV-1 RNA <50 copies/mL) and has received Health Canada’s approval in Mar’2020

Tuba:  Showcase the ViiV’s positive findings presented at the 2020 Infectious Diseases Society of America (IDSA) IDWeek.

Kimberly: At IDWeek 2020, we presented data across our innovative portfolio, showcasing meaningful advancements and scientific breakthroughs that are currently challenging the treatment paradigm. We shared positive findings across our development program for long-acting cabotegravir and rilpivirine, including five-year findings from LATTE-2 and 48-week findings from POLAR that further established the durable efficacy and safety of long-acting cabotegravir and rilpivirine. Findings from the implementation science CUSTOMIZE study showed that long-acting cabotegravir and rilpivirine was both acceptable and appropriate among people living with HIV and their providers, and provided best practices to integrate the investigational regimen in US healthcare settings. Lastly, positive findings from an analysis of the entire long-acting cabotegravir and rilpivirine development program confirmed there were no antiretroviral therapy interruptions in spite of COVID-19, demonstrating strong implementation fidelity for this potential HIV treatment option.

Tuba:  What are the impacts of global pandemic COVID-19 on the development of the dual regimen?

Kimberly: The analysis showed that no antiretroviral therapy interruptions were found across the entirety of the ongoing clinical development program for long-acting cabotegravir and rilpivirine. When missed visits occurred due to the pandemic, they were manageable and successfully mitigated, primarily by switching patients onto short periods of daily oral therapy of cabotegravir and rilpivirine, with no resulting virologic failure or emerging resistance. These findings speak to how the regimen of cabotegravir and rilpivirine may be adapted to meet the needs of people living with HIV who have events in their lives that could cause them to miss an injection appointment.

Tuba:  As the approval in the EU is on track, when can we expect the availability of a combination regimen in the EU?  What are your other geographical targets for seeking approval?

Kimberly: The long-acting regimen of cabotegravir and rilpivirine is currently under review by the US Food and Drug Administration and other global regulatory authorities.

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency’s (EMA) has issued a positive opinion recommending marketing authorization for long-acting cabotegravir and rilpivirine in both injectable and tablet formulations. The CHMP positive opinion is one of the final steps before marketing authorization is granted by the European Commission, which has the authority to approve medicines for use throughout the European Union.

Further regulatory authority submissions are planned in the coming months. We look forward to working with these regulatory authorities as part of our continued commitment to developing new and innovative treatment options for people living with HIV.

Tuba:  When can we expect the NDA submission of Cabotegravir and Rilpivirine complete long-acting regimen to the US FDA?

Kimberly: The long-acting regimen of cabotegravir and rilpivirine was resubmitted to the US Food and Drug Administration earlier this year and is currently under review. The PDUFA date is set for Jan. 28, 2021.

Tuba:  Is ViiV Healthcare working on any digital tool or planning to work on any digital initiative for changing the experience of people living with HIV?

Kimberly: ViiV Healthcare recently announced a new weekly podcast, Being Seen, which is an in-depth exploration of the role culture plays in resolving how we see ourselves and how we are seen by others. The first season explores current cultural representations of the queer and gay Black male experience and the impact on their lives and society.

Hosted and narrated by Darnell Moore, award-winning writer and activist, we hope that Being Seen can encourage more culturally accurate portrayals of the queer and gay Black male experience to reduce stigma and change perception. The podcast expands on insights and findings from our landmark ethnographic research conducted among Black gay men in Baltimore, Maryland and Jackson, Mississippi. We hope that this initiative will raise awareness to the impact of stigma on every aspect of these individual’s lives and underscore the collective responsibility to end discrimination among marginalized communities, including those living with HIV.

Tuba:  As ViiV Healthcare has a broad portfolio of medicines targeting HIV in adults, what are your efforts in pediatric HIV infection which is the most invisible population in HIV?

Kimberly: Age-appropriate formulations are essential to close the gap between treatment options available for adults and children and ensure children have access to life-saving medicines that give them the potential to be healthy, just like any other child.

On June 12, the FDA approved Tivicay PD tablets for oral suspension, which are used in combination with other antiretroviral agents for the treatment of HIV-1 infection in pediatric patients (treatment-naïve or -experienced but INSTI-naïve) aged at least four weeks and weighing at least 3kg. The FDA also approved the extended indication of already approved Tivicay 50mg film-coated tablet in pediatric HIV patients weighing 20kg and above.

In addition, we have worked in collaboration with the HIV community and our partners, DAIDS, NIH, IMPAACT, Penta, and MRC at UCL, who have been instrumental to our progress in generating and analyzing clinical data to optimize pediatric formulations and help improve the lives of children living with HIV.

About Kimberly Smith:

Dr. Kimberly Y. Smith MD, MPH is the Vice President for Global Medical Strategy and Head of Research and Development for ViiV Healthcare. She oversees the clinical development of the ViiV marketed and pipeline assets and works closely with the development teams in both GSK and Pfizer.

Related Post: ViewPoints Interview: Neoleukin’s Daniel-Adriano Silva Shares Insight on Novel Protein Designed to Treat or Block SARS-COV-2

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ViewPoints Interview: Neoleukin’s Daniel-Adriano Silva Shares Insight on Novel Protein Designed to Treat or Block SARS-COV-2

In a recent interview with PharmaShots Daniel-Adriano Silva, PhD, Co-founder and Vice President Head of Research at Neoleukin shared the significance and promise of the findings published in Science and discuss the details of its De Novo Protein Design

Shots:

  • NL-CVX1 (CTC-445.2d) demonstrated the ability to prevent infection of multiple human cell lines in vitro and to protect hamsters from serious consequences of SARS-CoV-2 infection
  • NL-CVX1 is designed to mimic the natural human ACE2 receptor. By doing so, it is designed to be resistant to viral mutation
  • De novo protein design begins computationally, where we identify the structure of the molecule we are trying to build and its interaction with the biological target

.

Tuba: Can we have an insight into Neoleukin’s research published in “Science”?

Daniel: The publication describes the potential of Neoleukin’s de novo protein design platform. In less than three months, our team was able to create novel molecules designed to treat or prevent infection by the virus that causes COVID-19, SARS-CoV-2. Specifically, it details the creation of de novo protein decoys that were designed to bind the SARS-CoV-2 spike protein with high affinity and prevent its association with the viral receptor hACE2, which is required for infection.

Our lead molecule, NL-CVX1 (CTC-445.2d), demonstrated the ability to prevent infection of multiple human cell lines in vitro and to protect hamsters from serious consequences of SARS-CoV-2 infection. Additionally, prophylactic intranasal administration of NL-CVX1 led to survival of all hamsters challenged with a lethal dose of SARS-CoV-2.

The full article “De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2”  can be accessed from the publications page of our website here.

Tuba: Tell us more about De Novo Protein Design?

Source: Neoleukin

Daniel: De novo protein design is a fundamentally different way to think about drug discovery.  Most traditional biologics are created by taking natural proteins and modifying them. De novo protein design begins computationally, where we identify the structure of the molecule we are trying to build and its interaction with the biological target.  These computational designs are then further refined and taken into the lab to be tested to evaluate whether the molecule demonstrates the desired properties.

This new way of protein engineering, called protein design, allows us to design proteins to have specific biologic activities and properties that provide potentially superior benefit over native proteins. Neoleukin Therapeutics is pioneering the application of de novo protein design to the development of therapeutic molecules.

Tuba: Discuss the potential of NL-CVX1 in protecting against SARS-CoV-2 infection?

Daniel: NL-CVX1 is designed to mimic the natural human ACE2 receptor.  By doing so, it is designed to be resistant to viral mutation.

In addition, NL-CVX1 is designed to be stable and could potentially be administered by intranasal spray or inhalation to prevent and treat infection in the lungs and upper airways by SARS-CoV-2.

Tuba: What can we learn about the potential of de novo protein design based on your experience in the development of NL-CVX1?

Daniel: NL-CVX1 was developed in less than three months from concept to preclinical validation. As such, we believe it represents the fastest development of a therapeutic de novo protein.  This rapid timeline demonstrates the potential of our de novo protein design platform to address a wide array of important biological problems.

Tuba: When can we expect NL-CVX1 (CTC-445.2d) to enter into clinical studies?

Daniel: We are currently evaluating the possibility of advancing this molecule to clinical trials in humans, as well as potential strategic partnership opportunities.

Tuba: Can we have a review on NeoLeukin’s lead program, NL-201 which is the world’s first computationally-designed de novo protein therapeutic?

Source: Neoleukin

Daniel: Our first program, NL-201, is a de novo receptor agonist of the IL-2 and IL-15 receptors, designed to expand cancer-fighting CD8 T cells and natural killer (NK) cells without any bias toward cells expressing the alpha receptor subunit (CD25). Previously presented preclinical data has demonstrated the ability of NL-201 to stimulate and expand CD8+ and NK cells at very low doses with minimal impact on immunosuppressive regulatory T cells. Treatment with NL-201 in animal models was well-tolerated and induced durable, anti-tumor immunity.  Additionally, minimal immunogenicity was reported following five weekly doses of NL-201 in non-human primates.

Our corporate update released on November 9, 2020 announced that we remain focused on our efforts to submit an Investigational New Drug (IND) application for NL-201 during the fourth quarter of 2020 and that we do not expect a delay in the submission of our IND due to COVID-19 but acknowledge the potential exists for this timing to be impacted. In addition, we have submitted a Clinical Trial Notification (CTN) application for NL-201 in Australia. The planned first-in-human clinical trials for NL-201 will test intravenous, monotherapy in patients with advanced solid tumors to determine the safety and tolerability of various dosing regimens.

Tuba: . Are you planning to collaborate with academia and industry to explore new applications of Neoleukins’ technology in other therapy areas or indications?

Daniel: De novo protein design is in its infancy, and we would welcome the opportunity to collaborate with academia and industry partners to move this technology forward.  We are focused on developing drugs in the oncology and autoimmune space.  However, given the potentially broad application of the technology, we would be open to exploring collaborations and other research efforts to design other molecules in areas outside oncology and autoimmune disease as well. 

While we are initially focused on establishing single agent activity for NL-201 in cancer, we recognize there may be an opportunity to combine NL-201 with other therapies such as checkpoint inhibitors, cell therapy, antibodies and other agents. 

About Daniel-Adriano Silva:

Daniel-Adriano Silva is aCo-founder and Vice President Head of Research at Neoleukin and is a leader in the fields of protein folding, structure, dynamics, and function and is the primary architect of the Neoleukin Platform.

Related Post: ViewPoints Interview: Kezar’s Noreen Henig Shares Insight on Therapeutic Potential of KZR-616

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ViewPoints Interview: Kezar’ Noreen Henig Shares Insight on Therapeutic Potential of KZR-616

In a recent interview with PharmaShots, Noreen Henig, Chief Medical Officer at Kezar Life Sciences shared information on clinical and pre-clinical data supporting the potential of KZR-616 to positively affect multiple drivers of immune-mediated diseases.

Shots:

  • The poster presented at ACR 2020 includes additional patient-weeks of safety and tolerability data compared to prior data presentations for our MISSION P-lb study in SLE patients with/out nephritis
  • No new safety signals have been observed and KZR-616 (SC, qw) has been consistently well tolerated for 13wks. Additionally, the company has started the enrollment in its P-ll PRESIDIO study for DM and PM
  • KZR-616 has the potential to reduce inflammation by targeting dysfunctional immune cells involved in autoimmunity without causing widespread immunosuppression in patients

Tuba: Can we have an overview of the posters presented at the American College of Rheumatology Annual Meeting (ACR) Convergence 2020?

Noreen: We presented both pre-clinical and clinical data with KZR-616, our first-in-class selective immunoproteasome inhibitor, during ACR. The presentation by Dr. Furie includes additional patient-weeks of safety and tolerability data compared to prior data presentations for our MISSION Phase 1b study in systemic lupus erythematosus (SLE) patients with and without nephritis. Encouraging trends in early efficacy signals continue, including improvement of SLE-specific disease activity scores and improvements in renal function and serum biomarkers in 2 of 2 patients with LN enrolled to the Phase 1b portion of the study. No new safety signals have been observed, and KZR-616 administered subcutaneously (SC) once weekly has been consistently well tolerated for 13 weeks. KZR-616 has been studied at doses of 45 mg, 60 mg, and 75 mg SC weekly. We previously identified 45 mg and 60 mg as likely therapeutic doses to advance in our clinical development program.

In a well-accepted preclinical mouse model of myositis, KZR-616 treatment was associated with significant improvement in muscle function and reduced levels of muscle tissue damage. It is also demonstrated that active immunoproteasome is necessary for the disease to occur. These data suggest that selective inhibition of the immunoproteasome with KZR-616 could have a meaningful clinical impact in patients with inflammatory myopathies, such as dermatomyositis (DM) and polymyositis (PM). We are actively enrolling the PRESIDIO Phase 2 study (NCT04033926), a placebo-controlled, cross-over study of patients with DM and PM. The open-label extension study (NCT04628936) for PRESIDIO is also enrolling. 

Source: Kezar

Tuba: How KZR-616 work to harmonize the immune system?

Noreen: Playing a critical role in the body’s immune system, the immunoproteasome is abundantly expressed in immune cells and acts as a master regulator of cellular function by degrading intracellular proteins. Selective inhibition of the immunoproteasome with KZR-616 has the potential to reduce inflammation by targeting dysfunctional immune cells involved in autoimmunity –, such as T -cells and B -cells –, without causing widespread immunosuppression in patients.

Source: Kezar

In doing so, KZR-616 has the potential to affect multiple drivers of immune-mediated diseases and harmonize the body’s immune system by restoring the immune response – almost like hitting the reset button on one’s immune system.

Tuba: Are you planning to explore the potential of KZR-616 beyond autoimmune disorders?

Noreen: Currently, we are focused on the autoimmune disorders of lupus nephritis, dermatomyositis, and polymyositis; however, we believe that there is strong scientific rationale to pursue KZR-616 for the treatment of a wide array of immune-mediated diseases and may do so in the future.

Tuba: When can we expect the results of the P-II portion of the MISSION study evaluating KZR-616 in patients with LN?

Noreen: We expect interim data towards the end of 2021 for the MISSION Phase 2.

Tuba: What are Kezar’s other programs in a pipeline to help patients overcome their disease and live a better life?

Noreen: We are pioneering research and discovery efforts targeting protein secretion pathways as potential therapies for oncology and immuno-oncology indications. We intend to submit an Investigational New Drug (IND) application for our first clinical candidate from this platform next year where we plan to target a number of difficult to treat solid tumors.

Tuba: When can we expect the results of P-II PRESIDIO & an OLE study?

Noreen: We expect top-line data from the PRESIDIO study in the first half of 2022 and the results from the open-label study would be available approximately 1 year later.

Tuba: What would be the targeted geographies for seeking approval of KZR-616?

Noreen: Autoimmune diseases have different prevalences across the globe, and our goal is to make this treatment available to as many people as possible and would intent to have a global registration plan but anticipate initially pursuing an FDA approval in the U.S.

Tuba: Are you looking for any collaborations for the launch of KZR-616?

Noreen: While this program does lend itself to potential collaboration based on its broad applicability in a wide array of immune-mediated diseases, we currently have the resources to develop KZR-616 on our own. 

Tuba: Is Kezar planning to develop a digital solution for immune-mediated diseases?

Noreen: We do not currently have plans to develop a digital solution for immune-mediated diseases.

About Noreen Henig:

Noreen R. Henig is the Chief Medical Officer at Kezar Life Sciences and the board member of Avidity Biosciences. Dr. Henig received a doctorate and a graduate degree from Albert Einstein College of Medicine and an undergraduate degree from Yale University.

Related Post: ViewPoints Interview: Cellares’ Fabian Gerlighaus Shares Insight on Cell Shuttle

The post ViewPoints Interview: Kezar’ Noreen Henig Shares Insight on Therapeutic Potential of KZR-616 first appeared on PharmaShots.

ViewPoints Article: Digital Biomarkers

The Healthcare industry is going through a technological revolution and it is vital for the industry to work on new technologies that will help to generate, collect & track novel data. The availability of large data makes the system becomes important to convert it into appropriate information which will helps industry researchers, clinicians, doctors, entrepreneurs, consumers to understand health and disease. Digital biomarkers provide an opportunity to interpret new data into informative & actionable insights.

BACKGROUND:

Biomarkers are characteristics (physiologic & pathologic) that can be objectively assessed and evaluated as an indicator of normal biological process, pathogenic process, or pharmacological response to therapeutic alteration inside the body. Digital biomarkers help in the collection of physiological & behavioral measures of the consumer using digital tools that can be used to explain & predict health-related outcomes. These outcomes can differ by the means of disease explanations to the prediction of drug response thereby influencing the fitness behavior of a person.

Figure 1: The role of digital biomarkers

In recent years companies such as Fitbit, Misfit, Jawbone, Apple health, MocaCare, Skeeper, etc which are into tracking sleep, fitness, blood pressure, etc. are growing fast. These companies become a substantial player in health & wellness, which are generating significant data not only about patients but also about individuals not on patient care. As per Market & Market data, the global marketplace for medical wearable devices is estimated to reach $12 billion by 2021. As these data-generating devices rise exponentially, the health care data also shows an astronomical growth rate. Patient-generated data using digital biomarkers provide new information in the healthcare industry.1

TYPES OF DIGITAL BIOMARKERS:

Digital biomarkers can be classified depending on the status of a particular measurement to a particular clinical outcome. Digital biomarker either replace non-digital biomarker (known as Approved), opens a new arena (Novel) or is a fusion/hybrid which on one hand substitute and on other hand unlocks new field (original).1

Figure 2: Classification of digital biomarkers

CURRENT APPLICATION OF DIGITAL BIOMARKERS:

Digital biomarkers can provide objective measurement which supports the diagnosis, prognosis, and measure therapeutic based outcomes. Currently, major pharma companies are running pilot studies to evaluate the feasibility of digital biomarker use. Roche has developed a Parkinson’s disease app to measure PD severity. Biogen in partnership with PatientsLikeMe developing an app to measure the physical activity of patients with multiple sclerosis whereas Neurotrack remotely assessed the cognitive ability of Alzheimer’s patients.

The outcome measures by using digital biomarkers in a clinical trial are limited but growing fast due to their precision & reliability. Recent years have observed the application of digital biomarkers in health areas such as cardiovascular disease, respiratory disorders, diabetes, neuropsychiatric disease, etc.

  1. Cardiovascular disease: Companies have engaged in the detection of atrial fibrillation for cardiovascular disease using algorithms based on smartwatch data. FDA has not approved algorithm-based data, but a digital biomarker for atrial fibrillation detection is available in conjunction with an approved EKG. Similarly, the study published in The New England Journal showed the use of accelerometer as the primary outcome measure in the treatment of congestive heart failure.2
  2. Sleep: Due to less validation requirement, a variety of digital biomarkers such as Fitbit’s sleep stages feature, MI Fit’ sleep score is commercially available. A study published in the journal Sleep in 2017, investigated the ability of wrist-worn tracker to estimate sleep stages in a normal adult. The result of the study demonstrated that the use of these devices can be used to track stages of sleep with reasonable accuracy in normal adults. These devices can simplify sleep research and will help to increase public awareness about sleep issues.3
  3. Respiratory Disorders: Smart inhalers for asthma and COPD consist of sensors that are attached to inhalers and monitor the use of medication. An objective assessment of inhaler adherence determined by obtaining the date, time & number of device actuation. These smart inhalers are Bluetooth-enabled and linked wirelessly with computers, tablets, or smartphones for automatic data transfer from inhalers. The companion mobile application gathers, interprets data & sends processed information to the healthcare professional. One of such FDA-approved applications developed by Propeller health known as Propeller health system which identifies the environmental triggers for patients with asthma, COPD & other respiratory conditions. It includes a sensor attached to a rescue inhaler or to a controller inhaler medication for effective management of the condition.4 Teva, another pharma company also launched FDA approved smart inhaler, Digihaler device in 2019 in the respiratory portfolio.5
  4. Diabetes: Diabetes is one of the major metabolic disorder which affect the large population worldwide. It always remained a highly innovative area in terms of digital therapeutics for pharma companies. San Francisco based company Omada Health; brought evidence-based digital therapeutics in the area of pre-diabetes/diabetes. The company offers a special online diabetes prevention program known as “Prevention” in association with the National Institutes of Health (NIH) which provides information regarding how diet and exercise reduce the chances of developing diabetes. During the program, each participant received a wireless digital scale and pedometer and interact with a personal health coach for daily feedback using an online platform. Results showed that participants lost 4.7% more body weight than an average weight loss of 2.4% for personal diabetes prevention programs.6 Merck & amazon partnership announced they are aiming to develop voice-enabled solutions for people with diabetes using Amazon’s Echo dot & Alexa.7
  5. Neuropsychiatric Disease: Different research programs are under progress in the area of neuropsychiatric disease. Researchers started examining wearables, accelerometers, and smartwatch devices in adults with Parkinson’s disease, Alzheimer’s disease, and dementia. Roche has developed a Parkinson disease application to capture voice-related information for obtaining early symptoms associated with Parkinson’s. Application collect voice data on phone & calculate stability when user hold devices.8

Neurotrack developed digital online test for detection of cognitive deficit in Alzheimer’s patient. The test is inexpensive & have potential of easy to use approach for detection of Alzheimer before development of clinical symptom. The test assessment are takes repeatedly so that user can track how memory changes over the time.9

CHALLENGES TO BE OVERCOME IN NEAR FUTURE10

  1. Standardized solutions: To compare & evaluate the results obtained during the studies by using digital biomarkers, standardized solutions are needed. During clinical trials, the use of standardized procedures ensures similar sampling in every case and therefore results are comparable with another achievement. In the case of consumer-generated data, it is not evident. The measurement carried out by smartwatches or trackers could be completely different in each situation.
  2. Reliability: As not all digital biomarkers are FDA or CE approved, the reliability of the instrument is questionable.
  3. Measurement issue: The measurement details can be entirely distinct as individuals can measure (for eg ECG) with different tools at home.
  4. Privacy or regulatory issue: Ensuring privacy and autonomy is of prime importance as digital biomarkers send measured data directly to the company or researcher. The data use agreement for digital biomarker should be thoroughly followed and must be monitored by government authority.

CONCLUSION:

Continuous monitoring of healthy as well as diseased persons using digital biomarkers will bring new data to a healthcare professional on regular basis. In the past, many incidences occurred where the use of new technology leads to a paradigm shift in the medical field which enabled new questions and novel insights in the healthcare system. The use of digital biomarkers will not cause a shift in the medical paradigm but it will offer novel ways for the measurement of health status which provides observations and perspectives into a disease that were unavailable before. Digital biomarkers will help to provide supplementary information & augment conclusions obtained from traditional biomarkers. The detailed measurement along with accurate & precise evaluation from molecular characterization of the disease using digital biomarkers will help to redefine diagnosis and classification of disease. The molecular profiling of disease with the help of digital biomarker can further support precision medicine & leads to innovative treatment in different disease. Finally, digital biomarkers not only provide information about what we know about the disease but also about understanding of their own health.  

REFERENCES:

  1. Traditional and Digital Biomarkers: Two Worlds Apart?
  2. Accelerometer-Measured Daily Activity in Heart Failure With Preserved Ejection Fraction
  3. 0068 ESTIMATION OF SLEEP STAGES USING CARDIAC AND ACCELEROMETER DATA FROM A WRIST-WORN DEVICE
  4. Propeller
  5. Teva Announces FDA Approval of First and Only Digital Inhaler with Built-In Sensors – ProAir Digihaler (albuterol sulfate 117 mcg) Inhalation Powder
  6. Omadahealth
  7. Merck aims to put Amazon’s Alexa to work on voice-enabled diabetes tools
  8. Roche will use the app to track Parkinson’s symptoms in drug trial
  9. Neurotrack
  10. Digital technologies as biomarkers, clinical outcomes assessment, and recruitment tools in Alzheimer’s disease clinical trials.

About Co-Author:

Sunaina Anand

Dr. Sunaina Anand, Pharm. D is a Clinical Pharmacist. She currently serves as Medical Affairs Executive in IntelliMed Healthcare Solutions. She previously interned in Tata Memorial Hospital and Columbia Asia Hospital, Bengaluru.

The post ViewPoints Article: Digital Biomarkers first appeared on PharmaShots.

ViewPoints Interview: Cellares’ Fabian Gerlighaus Shares Insight on Cell Shuttle

In a recent interview with PharmaShots, Fabian Gerlighaus, Co-Founder and CEO of Cellares, shared information on Cellares partnership with Fred Hutchinson Cancer Research Center and unveils how the company is working to get patients the cell therapies they need.

Shots:

  • Cellares’ collaboration with Fred Hutchinson Cancer Research Center is a part of EAPP. Fred Hutch will work closely with Cellares by providing insights into manufacturing workflows for CAR-T cell therapies, natural killer cell therapies, and other cell therapy modalities
  • The Cell Shuttle is the first industrial scale cell therapy manufacturing solution
  • The main impact Cellares will have is to accelerate access to life-saving cell therapies, by making them more affordable and widely available to patients in need

Tuba: Can we have detail on Cellares collaboration with Fred Hutchinson Cancer Research Center?

Fabian: Cellares’ collaboration with Fred Hutchinson Cancer Research Center is a part of our Early Access Partnership Program (EAPP). As a partner, Fred Hutch will work closely with Cellares by providing insights into manufacturing workflows for CAR-T cell therapies, natural killer cell therapies, and other cell therapy modalities. The Center will also participate in user studies, inform system specifications, and provide feedback on Cellares’ proprietary platform to help ensure product-market fit.

Tuba: Are you looking for more organizations to join your Early Access Partnership Program?

Fabian: We are currently in talks with multiple organizations for the EAPP and are very excited about the potential of growing this program with other top tier organizations in the field. At this time, we cannot disclose any more details as conversations are ongoing but will be sure to share future updates with you when we can.

Tuba: Please tell us more about the Cell Shuttle. How it is helping Cellares to make cell therapy widely available and affordable?

Source: Cellares

Fabian: Most cell therapies today are produced for a single patient at a time, using that patient’s cells as the starting material. This current process of one dose at a time is very labor-intensive, failure-prone, and extremely difficult to scale with manual methods. Many indications have patient populations of tens of thousands of doses per year, but due to the lack of automated and scalable manufacturing technologies, even the most pioneering cell therapy companies struggle to treat a few thousand patients per year.

The Cell Shuttle is the first industrial-scale cell therapy manufacturing solution. It is a factory-in-a-box that offers true walk-away end-to-end automation – from loading a patient’s cells to unloading a cell therapy dose ready for infusion. In contrast to any other cell therapy manufacturing solution on the market today, it has the ability to produce up to 10 patient doses simultaneously. This is an order of magnitude improvement in instrument throughput, which is what is required to help our customers scale-out manufacturing from a few thousand doses annually per drug to tens of thousands of doses annually per drug. In this way, Cellares is helping the industry to make cell therapies widely available for patients.

Another hurdle is the risk of process failure. Many cell therapies today are made-to-order for patients who are terminally ill and have fully exhausted other treatment options. A critical process failure can lead to the loss of a patient’s life, because there may not be another opportunity to collect high-quality starting material from the patient for a second attempt. Through automating and closing the manufacturing process, the Cell Shuttle enables a three-fold reduction in process failure rates by eliminating opportunities for operator error and contamination.

Because the Cell Shuttle maintains its own cleanroom environment it can be deployed in lower-class environments, which have a significantly lower cost per square foot. It also reduces the amount of cleanroom space that’s required by about 80 percent compared with manual methods, allowing for smaller manufacturing sites with higher productivity. By automating the entire manufacturing process end-to-end, further reduces the amount of human labor by up to 75 percent for many cell therapy workflows. Overall, we’re confident that we can reduce manufacturing costs by up to 70 percent compared with manual methods, making cell therapies more affordable over time.

Tuba: What makes Fred Hutch an ideal partner to develop Cellares’ manufacturing platform?

Fabian: For more than four decades researchers at the Hutch have been pioneering treatments for cancer, from the work of Nobel laureate Dr. E. Donnall Thomas to the breakthroughs achieved by Dr. Phil Greenberg, an internationally recognized expert in cancer immunotherapy. The Hutch co-founded Juno Therapeutics in 2013, another leading cell therapy company, and they have a full pipeline of clinical trials including CAR-T cell therapies, natural killer cell therapies, and other cell therapy modalities. As such, they are an ideal partner to provide insights and feedback on our novel technology and ensure it overcomes the challenges with cell therapy manufacturing for the benefit of patients around the world. We have tremendous respect for the organization and are proud to be working with them to advance our mission of accelerating access to life-saving cell therapies.

Tuba: Is Cellares planning to raise more funding in the near future to build its manufacturing technology?

Fabian: To date, we’ve raised $18 million in a Series A financing led by Eclipse Ventures, with participation from 8VC and EcoR1 Capital. As the CEO, I’m always looking ahead to ensure we have the resources we need to accelerate our mission and make a profound impact on the future of cell therapy manufacturing. We will be sure to share additional financial updates at the appropriate time.

Tuba: How can Cellares make an impact on the future of cell therapy manufacturing?

Fabian: The main impact Cellares will have is to accelerate access to life-saving cell therapies, by making them more affordable and widely available to patients in need.

Additionally, in the context of preclinical process development, the Cell Shuttle enables the high-throughput design of experiment (DOE) studies in scale-down models to generate insights that help determine the best possible process parameters for each cell therapy workflow. In this way, Cellares is building a single technology platform that meets our customer’s needs from the preclinical phase, through the clinic, and all the way to commercial-scale manufacturing. Avoiding the need to change manufacturing platforms, as is usually required, eliminates laborious and expensive technology transfer processes, accelerating market entry by more than a year. The impact that we’re hoping to have is to provide patients with access to life-saving cell therapies earlier than they otherwise would.

Finally, there may be an impact on the split between autologous and allogeneic methods. One of the main drivers for allogeneic cell therapy is to increase the number of doses per batch, thus decreasing the cost. That said, autologous approaches have several advantages from a clinical perspective, they’re generally safer and the therapeutic effect is more enduring. While the cutting-edge technology we’re developing will support both autologous and allogeneic approaches, I firmly believe that it has the potential to make autologous cell therapy manufacturing much more cost-effective and scalable.

Tuba: “Cellares’ revolutionary technology will be a game-changer for the cell therapy industry.’’ Comment on the statement.

Fabian: Hearing Dr. Carl June, the pioneer of the first FDA approved CAR-T cell therapy, Kymriah, say that the technology we are building is “gaming changing” was a huge vote of confidence. He had just finished reviewing our system architecture in detail when he said this. It certainly solidified the confidence in our approach and further increased our excitement to bring this technology to our customers and help patients.

Tuba: How is the Cellares’ manufacturing technology different from currently available cell therapy manufacturing methods?

Fabian: The Cell Shuttle is different from currently available cell therapy manufacturing methods in a number of ways. Most notably it’s the first solution that allows our customers to scale out to treat tens of thousands of patients annually per drug, without compromising on process flexibility.

The semi-automated systems on the market today lock you into very rigid and narrowly defined workflows. This is very limiting to customers because in cell therapy the product is the process. Cellares is shifting this paradigm by providing biopharma companies, academic research centers and CDMOs with a fully automated platform that integrates modular hardware with flexible software.

The Cell Shuttle has an incredibly modular system architecture so you can configure which processing technologies are on your platform when you order it and even change it thereafter. The modular hardware works in conjunction with a powerful software suite that enables process development scientists to quickly design and execute bespoke cell therapy manufacturing workflows. Users can effortlessly drag and drop cell therapy manufacturing steps into the order that best suits their unique process. In addition, they have full control over all of the underlying process parameters & visibility into a vast amount of data collected throughout the process. We are putting the power back into the hands of our customers, instead of requiring them to work with external application teams for every protocol change. This is how Cellares offers the best of both worlds—automation and flexibility.

In the absence of better options, the field has come to rely on companies which make incremental improvements to benchtop instruments that handle one or two processing steps for a single patient at a time. Our scope is much larger. We are providing an end-to-end solution, from loading the apheresis, to automating cell enrichment, cell selection, cell activation, gene transfer, expansion, fill, finish and formulation. What you’re unloading at the very end is a cell therapy dose ready for release testing & infusion into the patient.

Finally, one of the biggest differentiators of the Cell Shuttle is its capacity to produce up to 10 unique patient doses simultaneously. This is an order of magnitude improvement in throughput compared with any other manufacturing solution on the market today. True end-to-end automation in combination with high throughput is what makes the Cell Shuttle the first solution that enables manufacturers to scale out to meet patient demand.

Tuba: Is Cellares working on more solutions to overcome the limitations associated with the manufacturing of cell therapies?

Fabian: Right now, we are focusing our attention on continuing the development of the Cell Shuttle to help our customers lower manufacturing costs, accelerate market entry, and scale-out production to meet patient demand. Our long term roadmap includes additional developments that will further the Cellares vision of enabling safe and affordable access to cell therapies for all patients.

Tuba: Do you feel competition in this space? If yes, who would be your potential competitor?

Fabian: There are other companies providing limited automation of some cell therapy workflows.  However, no other technology that we are aware of offers true end-to-end automation, in a closed and flexible platform that is cost-effective and reliable and can scale to tens of thousands of patients annually per drug. This unlocks significant additional revenue for our customers and provides patients with affordable access to life-saving cell therapies. At Cellares we are building the future of cell therapy manufacturing.

About Fabian Gerlighaus:

Fabian Gerlighaus is a Co-Founder and CEO of Cellares. With 10+ years of experience as an innovator and a leader, Fabian has established a track record of assembling top-performing teams to successfully drive novel bioprocessing technologies from ideation to commercial readiness.

Related Post: ViewPoints Interview: Novocure’s William F. Doyle Shares Insight on Company’s Accomplishments in the Treatment of Glioblastoma and Mesothelioma

The post ViewPoints Interview: Cellares’ Fabian Gerlighaus Shares Insight on Cell Shuttle first appeared on PharmaShots.

ViewPoints Interview: Novocure’s William F. Doyle Shares Insight on Company’s Accomplishments in the Treatment of Glioblastoma and Mesothelioma

In a recent interview with PharmaShots, William F. Doyle, Executive Chairman at Novocure shared information about the company’s activities in the field of glioblastoma and mesothelioma. He also discussed the company’s technology, Tumor Treating Fields (TTFields), and its potential for broad applicability across solid tumors.

Shots:

  • Novocure is a global oncology company working to extend survival in aggressive forms of cancer through the development & commercialization of our innovative therapy, Tumor Treating Fields, also known as TTFields
  • TTFields are low-intensity, wave-like electric fields. These invisible electric fields are not strong enough to hurt you or your healthy cells, but they are strong enough to slow or stop cancer cells from dividing (splitting apart. When a cancer cell divides, it creates even more cancer cells
  • Novocure has grown from a market cap of $1.87B in 2015 to over $10B currently – a nearly 500% increase

Tuba: Please tell us about your company, its mission and how it is reimagining your industry? 

William: Novocure is a global oncology company working to extend survival in some of the most aggressive forms of cancer through the development and commercialization of our innovative therapy, Tumor Treating Fields, also known as TTFields.

Novocure’s commercialized products are approved in certain countries for the treatment of adult patients with glioblastoma, or GBM, and for the treatment of adult patients with malignant pleural mesothelioma, or MPM.

Our company is reimagining the industry by putting patients first in our goal to deliver innovative cancer therapy.

Tuba: How would you describe Novocure’s clinical pipeline and overall product portfolio?

William: We believe our mechanism of action is broadly applicable across a variety of solid tumors. Currently, we are focused on cancers of the brain, torso and abdomen.

Our Optune® device is currently approved for two indications of Glioblastoma, also called glioblastoma multiforme, which is the most aggressive type of malignant primary brain tumor. In 2019, we received our first torso indication with the approval of the Optune Lua ® device to help treat malignant pleural mesothelioma, a tumor of the tissue that lines the lungs, stomach, heart, and other organs.

With a focus on treating rare and aggressive cancers, we are also studying our Tumor Treating Fields technology in 6 additional indications, including four late-stage clinical trial programs in brain metastasis, non-small cell lung cancer, pancreatic cancer and ovarian cancer.

We continue the effort to extend our pipeline by building pre-clinical evidence for Tumor Treating Fields in additional solid tumor cancers

Tuba: What are Tumor Treating Fields (TTFields) and how do they help fight the most deadly cancers?

Source: Novocure

William: TTFields are low-intensity, wave-like electric fields. These invisible electric fields are not strong enough to hurt you or your healthy cells, but they are strong enough to slow or stop cancer cells from dividing (splitting apart. When a cancer cell divides, it creates even more cancer cells. TTFields may destroy some cancer cells completely TTFields but have not been shown to affect healthy cells.

Tuba: I hear you are celebrating a couple of different 5-year anniversaries for both your IPO and an FDA approval in glioblastoma. How have you seen the glioblastoma business change and grow since that approval?

A4: Shortly after our IPO, we began our commercial launch for our second Indication in GBM in the U.S. and our device is now marketed in eight active markets, the U.S., Austria, Germany, Israel, Japan, Sweden, Switzerland and most recently in China. To date, we have treated more than 17,000 patients globally with 3,361 active patients on Optune at the end of Q3 2020. Additionally, we have broadened access to Optune with more than 500 million covered lives globally. 

Tuba: From a financial standpoint, how have you seen the company evolve in the past five years?

William: Novocure has grown from a market cap of $1.87 billion in 2015 to over $10 billion currently – a nearly 500% increase. 

Most recently, Novocure announced that the company delivered another record quarter of financial performance, with net revenues for the quarter ending September 30, 2020, at $132.7 million, representing 44% growth compared to the third quarter of 2019. We also had a quarterly net income of $9.3M with a $0.09 in earnings per share in Q3 2020.

Our investment in R&D to support the continued advancement of Tumor Treating Fields’ science and technology has also grown.  In Q3 2020, we invested $33M in R&D in comparison to $19M in Q3 2019.

Tuba: Can you tell us about some ongoing collaborations, specifically your recently announced strategic alliance with the NYU Grossman School of Medicine’s Department of Radiation Oncology?

William: Zai Lab’s early launch of Optune in China in 2020 was a success. The goal of this collaboration was to commercialize Optune in mainland China, as well as to accelerate development in other solid tumor indications. It became the first innovative medical device supported by commercial health insurance in China.

Additionally, we recently announced our alliance with the NYU Grossman School of Medicine’s Department of Radiation. The partnership establishes NYU as a center for Tumor Treating Fields’ research and development. The goal of the collaboration is to expand understanding of the interaction between Tumor Treating Fields and radiation therapy, to study Tumor Treating Fields in combination with various pharmacological agents, and to identify new indications for use. This translational research is intended to deepen the understanding of Tumor Treating Fields’ effects on cancer and to fuel the development of new treatment strategies.

Tuba: What do you like best about working at Novocure?

William: At Novocure, patients remain at the heart of the work we do every day.  What I like best about working at Novocure is having the ability to help drive the company’s efforts in the development and delivery of a completely different type of cancer therapy that could lengthen the lives of patients while maintaining their quality of life. 

About William F. Doyle:

 William F. Doyle is an Executive Chairman at Novocure 2009 and has been a director since 2004.

Related Post: ViewPoints Interview: Medtronic’s Julie Foster Shares Insight on InPen Integrated with Guardian Connect CGM

The post ViewPoints Interview: Novocure’s William F. Doyle Shares Insight on Company’s Accomplishments in the Treatment of Glioblastoma and Mesothelioma first appeared on PharmaShots.

ViewPoints Interview: Medtronic’s Julie Foster Shares Insight on InPen Integrated with Guardian Connect CGM

In a recent interview with PharmaShots, Julie Foster, Vice President, Global Customer Experience of the Diabetes business at Medtronic, shares information about recent and upcoming announcements for the company.

Shots:

  • The integration of real-time CGM data into the smart insulin pen app follows the acquisition of Companion Medical’s InPen to the Medtronic portfolio, as of Sept’2020
  • The integrated system provides real-time glucose readings alongside insulin dose information giving users everything they need to manage their diabetes through a single smartphone app
  • InPen is the first and only FDA-cleared smart2 insulin pen on the market for people on MDI. The InPen app will continue to display information from other compatible CGM systems on a three-hour delay

Tuba: Medtronic has been taking some big steps to grow its diabetes portfolio with the purchase of Klue, Nutrino, and Companion Medical. What new capabilities does this give the company?

Julie: We are working to ‘close the loop for MDI’ patients. By combining smartpen with smart CGM technologies, we aim to deliver proactive dosing advice personalized to each individual. We acquired Nutrino and Klue to enable the future of diabetes therapy through artificial intelligence: Nutrino helps us improve our predictive analytic capabilities around mealtimes, and with the identification of what’s being consumed with greater accuracy. Klue’s gesture technology helps identify when that food is being consumed. Our goal is to combine AI technology and our extensive CareLink database of real-life data to develop technologies that we can leverage across all of our insulin delivery platforms — both pen and pump.

Tuba: Medtronic recently announced the launch of InPen integrated with real-time Guardian Connect CGM data. Can you explain the benefits of this integrated system?

Julie: Every person’s journey with diabetes is different, and we want to provide options for each individual that meet their needs. An example is this integrated system, which now provides real-time glucose readings alongside insulin dose information, giving users everything they need to manage their diabetes in one view as a complete picture, rather than switching between apps to understand their in-the-moment dosing needs. We want to help make life easier for people living with diabetes, and by building on the success of InPen with added real-time glucose data, we hope we’ve done just that.

https://pharmashots.com/36893/kiniksas-rilonacept-receives-the-us-fdas-orphan-drug-designation-treat-pericarditis/

Tuba: Can you share some details about Medtronic’s newest insulin pump system; the MiniMed 770G hybrid closed loop system? How is it different?

Julie: The MiniMed 770G system builds on the successful MiniMed 670G systems as it adds smartphone connectivity and an expanded age indication to children as young as two. Having a young child diagnosed with diabetes can be scary for parents, so we hope the use of this system will provide some peace of mind by enabling them to monitor their child’s sugars and pump details at any time on their phone.

Tuba: What is Medtronic’s philosophy for working together with customers? What role does customer feedback play in innovation?

Julie: Our customer experience philosophy boils down to, “Diabetes Takes No Breaks. Neither Do We. Always By Your Side.” Those living with type 1 diabetes never get to take a break from managing the disease – it is an around-the-clock job, so learning from patient experiences is the most critical way to drive our future products. For example, listening to the struggles parents face when their young child is diagnosed with type 1 helped us in the development and launch of the MiniMed 770G.  Based on continual feedback from our customers, we are deeply committed to continue advancing services and solutions for those working with Medtronic have the best experience possible. 

Tuba: Medtronic recently launched a CGM Access Discount program. Can you tell us more about the program, and how it differs or compliments the proposed updates from the Centers for Medicare & Medicaid Services to expand CGM coverage?

Julie: We are very encouraged by CMS’s proposed rule and commend the agency on taking action to help more people with diabetes. The proposal puts patients first and empowers them to choose what best meets their diabetes management needs. While the proposed CMS rule is under review, Medtronic is offering a CGM Access Discount program, which allows users without insurance coverage, or those who switched insurance and lost coverage, to access a discounted out-of-pocket cost for a Medtronic CGM. More information about that program can be found here.

Tuba: For diabetics, the dream of one day having a fully automated artificial pancreas is becoming more real with new technologies. How close do you think we are to this achievement?

Julie:  From the discovery of insulin, now almost at its centennial, to the evolution of insulin pumps beginning the 1960s, to advancements currently in development, the history of diabetes management is an amazing one. We were the first to put an automated insulin delivery system on the market, but we know we have much work to do and are committed to continual improvement and advancement of the technology, services, and solutions we offer.  

I can’t predict the future, yet one thing I can say with great confidence is that we will work tirelessly toward a world in which people with diabetes can live more freely without needing to think about managing their disease all the time. It is deeply aligned with our mission and our inspiration.

About Julie Foster:

Julie Foster is the Vice President, Global Customer Experience of the Diabetes business at Medtronic. Foster has been at Medtronic for over 30 years across multiple businesses, therapeutic areas, and regions, and holds degrees from the University of St. Thomas and the University of San Diego.

Related Post: ViewPoints Interview: Duke’s Andrea Taylor Shares Insight on Launch And Scale Speedometer

The post ViewPoints Interview: Medtronic’s Julie Foster Shares Insight on InPen Integrated with Guardian Connect CGM first appeared on PharmaShots.

ViewPoints Interview: Medtronic’s Julie Foster Shares Insight on InPen Integrated with Guardian Connect CGM

In a recent interview with PharmaShots, Julie Foster, Vice President, Global Customer Experience of the Diabetes business at Medtronic, shares information about recent and upcoming announcements for the company.

Shots:

  • The integration of real-time CGM data into the smart insulin pen app follows the acquisition of Companion Medical’s InPen to the Medtronic portfolio, as of Sept’2020
  • The integrated system provides real-time glucose readings alongside insulin dose information giving users everything they need to manage their diabetes through a single smartphone app
  • InPen is the first and only FDA-cleared smart2 insulin pen on the market for people on MDI. The InPen app will continue to display information from other compatible CGM systems on a three-hour delay

Tuba: Medtronic has been taking some big steps to grow its diabetes portfolio with the purchase of Klue, Nutrino, and Companion Medical. What new capabilities does this give the company?

Julie: We are working to ‘close the loop for MDI’ patients. By combining smartpen with smart CGM technologies, we aim to deliver proactive dosing advice personalized to each individual. We acquired Nutrino and Klue to enable the future of diabetes therapy through artificial intelligence: Nutrino helps us improve our predictive analytic capabilities around mealtimes, and with the identification of what’s being consumed with greater accuracy. Klue’s gesture technology helps identify when that food is being consumed. Our goal is to combine AI technology and our extensive CareLink database of real-life data to develop technologies that we can leverage across all of our insulin delivery platforms — both pen and pump.

Tuba: Medtronic recently announced the launch of InPen integrated with real-time Guardian Connect CGM data. Can you explain the benefits of this integrated system?

Julie: Every person’s journey with diabetes is different, and we want to provide options for each individual that meet their needs. An example is this integrated system, which now provides real-time glucose readings alongside insulin dose information, giving users everything they need to manage their diabetes in one view as a complete picture, rather than switching between apps to understand their in-the-moment dosing needs. We want to help make life easier for people living with diabetes, and by building on the success of InPen with added real-time glucose data, we hope we’ve done just that.

https://pharmashots.com/36893/kiniksas-rilonacept-receives-the-us-fdas-orphan-drug-designation-treat-pericarditis/

Tuba: Can you share some details about Medtronic’s newest insulin pump system; the MiniMed 770G hybrid closed loop system? How is it different?

Julie: The MiniMed 770G system builds on the successful MiniMed 670G systems as it adds smartphone connectivity and an expanded age indication to children as young as two. Having a young child diagnosed with diabetes can be scary for parents, so we hope the use of this system will provide some peace of mind by enabling them to monitor their child’s sugars and pump details at any time on their phone.

Tuba: What is Medtronic’s philosophy for working together with customers? What role does customer feedback play in innovation?

Julie: Our customer experience philosophy boils down to, “Diabetes Takes No Breaks. Neither Do We. Always By Your Side.” Those living with type 1 diabetes never get to take a break from managing the disease – it is an around-the-clock job, so learning from patient experiences is the most critical way to drive our future products. For example, listening to the struggles parents face when their young child is diagnosed with type 1 helped us in the development and launch of the MiniMed 770G.  Based on continual feedback from our customers, we are deeply committed to continue advancing services and solutions for those working with Medtronic have the best experience possible. 

Tuba: Medtronic recently launched a CGM Access Discount program. Can you tell us more about the program, and how it differs or compliments the proposed updates from the Centers for Medicare & Medicaid Services to expand CGM coverage?

Julie: We are very encouraged by CMS’s proposed rule and commend the agency on taking action to help more people with diabetes. The proposal puts patients first and empowers them to choose what best meets their diabetes management needs. While the proposed CMS rule is under review, Medtronic is offering a CGM Access Discount program, which allows users without insurance coverage, or those who switched insurance and lost coverage, to access a discounted out-of-pocket cost for a Medtronic CGM. More information about that program can be found here.

Tuba: For diabetics, the dream of one day having a fully automated artificial pancreas is becoming more real with new technologies. How close do you think we are to this achievement?

Julie:  From the discovery of insulin, now almost at its centennial, to the evolution of insulin pumps beginning the 1960s, to advancements currently in development, the history of diabetes management is an amazing one. We were the first to put an automated insulin delivery system on the market, but we know we have much work to do and are committed to continual improvement and advancement of the technology, services, and solutions we offer.  

I can’t predict the future, yet one thing I can say with great confidence is that we will work tirelessly toward a world in which people with diabetes can live more freely without needing to think about managing their disease all the time. It is deeply aligned with our mission and our inspiration.

About Julie Foster:

Julie Foster is the Vice President, Global Customer Experience of the Diabetes business at Medtronic. Foster has been at Medtronic for over 30 years across multiple businesses, therapeutic areas, and regions, and holds degrees from the University of St. Thomas and the University of San Diego.

Related Post: ViewPoints Interview: Duke’s Andrea Taylor Shares Insight on Launch And Scale Speedometer

The post ViewPoints Interview: Medtronic’s Julie Foster Shares Insight on InPen Integrated with Guardian Connect CGM first appeared on PharmaShots.

ViewPoints Interview: Duke’s Andrea Taylor Shares Insight on Launch And Scale Speedometer

In a recent interview with PharmaShots, Andrea Taylor, Researcher at Launch And Scale Speedometer shared her insights and highlights on data how rich countries’ shopping spree for COVID-19 vaccines means fewer vaccinations for billions in low-income countries

Shots:

  • The Launch and Scale Speedometer project aims to systematically analyze the factors that support or hinder the introduction and scaling of interventions, including but not limited to drugs, diagnostics, and devices, to address critical global health challenges
  • The Covax Facility is currently the only mechanism to bring low-income countries into the market and ensure equitable access to successful vaccine
  • The study reveals that while it will likely take 3-4years to manufacture enough vaccines to cover the world’s population, close to 7B doses of COVID-19 vaccine candidates are already being negotiated through deals involving mainly high-income countries, vaccine developers and global vaccine manufacturers

Tuba: How high-income countries are creating a threat to low-income countries’ ability to access future vaccines for COVID-19?

Andrea: The issue is that, because of global manufacturing constraints, every direct deal made by high-income countries takes doses off the future market. This means that very little may be left by the time vaccines actually come to market and that low-income countries, which aren’t able to make advance purchases, may lose out. It may be two or three years before we are able to manufacture enough doses to cover even high priority populations in low-income countries, while high-income countries may get first access to the doses that are produced in the first year or two.

Tuba:  Can we have detail on the analysis done by Duke Global Health Innovation Center?

Andrea: We have provided detailed analysis on our website: https://launchandscalefaster.org/COVID-19. I am happy to answer any specific questions you might have about our analysis.

Tuba:  Could you please share in detail about Launch And Scale Speedometer?

Andrea: The Launch and Scale Speedometer project aims to systematically analyze the factors that support or hinder the introduction and scaling of interventions, including but not limited to drugs, diagnostics, and devices, to address critical global health challenges. The primary goals of this project are to:

  • obtain high-quality data on launch and scale-up trends of health interventions globally;
  • generate and share valuable insights to improve launch and scale pathways; and,
  • increase collaboration and accountability across the health sector for achieving efficiency and effectiveness for launch and scale so that interventions reach the people who need them more quickly and efficiently.

As part of this project, we have launched a focused workstream on the development and distribution of vaccines, therapeutics, diagnostics and other interventions related to combating the COVID-19 pandemic.

Tuba:  How Launch and Scale Speedometer help the equitable allocation of COVID-19 vaccines globally?

Andrea: We are mapping the advance purchases made globally to provide transparency and insight into the flow of purchase agreements. Our findings indicate a pattern of purchasing by high-income countries that may undermine the commitment to equity made by these same countries. Equitable allocation appears to be at risk, given the number of doses already reserved before any vaccine candidates are even on the market. Our findings serve as a warning and we hope that our analysis will inform investments in mechanisms that promote equity, such as the Covax Facility, as well as increasing manufacturing capacity, particularly in low- and middle-income countries. We will update our advance purchase data every two weeks and continue research into additional areas such as manufacturing capacity, partnerships, and distribution strategies.

Tuba:  8.8B Doses are already reserved, even before any candidate in the market. Comment over the statement.

Andrea: As I noted above, this is an issue in light of the global manufacturing constraints. Despite generous investments in equity through support of the Covax Facility, many high-income countries have also made direct deals to purchase large numbers of vaccine, in some cases enough to cover their populations several times over. This undermines their investment in equity by removing doses from the market before we can ensure that all countries have access to enough to cover the high-priority populations. However, we can mitigate the impact of this somewhat by increasing manufacturing capacity.

Tuba: Can we have an insight on the confirmation status of vaccine doses procured by the Country’s income level?

Andrea: What our findings show is that high-income countries have been very successful in purchasing a portfolio of vaccine candidates, increasing the chance that at least one of these investments will come to market. A few middle-income countries have also been successful in making advance purchases, particularly those with manufacturing capacity, such as India and Brazil. We have also seen middle-income countries leveraging participation in clinical trials to secure advance deals for vaccine candidates. However, low-income countries have been left out of this market entirely.

Tuba: What are the critical challenges facing by low-income countries like Ethiopia and Peru in the distribution of vaccines?

Andrea: Peru is actually a middle-income country and has been able to secure advance market purchases, in part by leveraging participation in clinical trials. But both middle- and low-income countries will face significant challenges in distribution. These include poor cold-chain infrastructure (particularly an issue for vaccine candidates requiring freezer or supercold storage temperatures), large populations living in remote areas far from healthcare providers, and immunization programs designed to target newborns and children, rather than the elderly. In addition, some countries are facing significant issues with misinformation about COVID-19 that may impact take-up of vaccines.

Tuba: What you think can help low income & middle-income countries to secure vaccine doses?

Andrea: The Covax Facility is currently the only mechanism we have to bring low-income countries into the market and ensure equitable access to successful vaccines. There are at least two additional strategies, though, that can help to strengthen the positions of low- and middle-income countries. The first is to unlock additional manufacturing capacity in low- and middle-income countries, particularly in sub-Saharan Africa. This is no guarantee but makes it more likely that manufactured doses will stay on the continent. The second strategy is for low- and middle-income countries to pool financing and procurement as a regional block. For example, the African Union and the Africa CDC are developing a “whole-Africa” approach that aims to raise $5 billion to purchase vaccines that can be distributed across African countries. While these countries individually have been unable to compete on the advance purchase market, they will have a stronger position and purchasing power as a block.

Tuba: Approximately 200 Covid-19 candidates are in development, who you think are leaders in developing vaccines of COVID-19? When can we expect the first vaccine for COVID-19?

Andrea:   It looks likely that the first vaccines will begin to ship out by March of 2021. The vaccine candidates developed by Pfizer/BioNTech and Oxford/Astra Zeneca appear to be closest to receiving regulatory approval. However, the first vaccines to cross the regulatory finish line will not necessarily be the best candidates, particularly for low- and middle-income countries. Several of the leading candidates in terms of timeline are two-dose vaccines that require freezer or ultracold storage, which will be difficult or impossible for many countries to implement, particularly in rural and remote regions. These may be followed closely by one-dose vaccine candidates that only need standard refrigeration or, better yet, a “warm” vaccine, both of which are currently being tested. These vaccine candidates would be much better investments from the perspective of low- and middle-income countries, in terms of being easier to implement and reducing wastage.

About Andrea Taylor:

Andrea Taylor, Researcher at Launch And Scale Speedometer and led the analysis for the Launch and Scale initiative.

Related Post: ViewPoints Interview: FibroGen’s Peony Yu Shares Insight on Roxadustat

The post ViewPoints Interview: Duke’s Andrea Taylor Shares Insight on Launch And Scale Speedometer first appeared on PharmaShots.

ViewPoints Interview: FibroGen’s Peony Yu Shares Insight on Roxadustat

In a recent interview with PharmaShots, Peony Yu, Chief Medical Officer of FibroGen shared her insights and highlights on data of Roxadustat

Shots:

  • FibroGen presented new efficacy and safety analyses from the roxadustat global P-III program at ASN Kidney Week 2020 Reimagined. FibroGen and its partners, AstraZeneca and Astellas, presented 42 abstracts, including 2 late-breaker poster presentations, and 10 oral presentations
  • The roxadustat clinical data demonstrated consistent efficacy and reassuring safety results across the continuum of CKD patients with anemia
  • FibroGen is pursuing groundbreaking research and science to drive forward a pipeline that may transform the patient experience and create new standards of care in anemia and an array of serious fibrotic conditions

Tuba: Can you briefly summarize the presentation & abstracts of P-III Global Program of roxadustat at ASN Kidney Week 2020 Reimagined?

Peony Yu: FibroGen presented new efficacy and safety analyses from the roxadustat global Phase 3 program at American Society of Nephrology (ASN) Kidney Week 2020 Reimagined. FibroGen and its partners, AstraZeneca and Astellas, presented 42 abstracts, including 2 late-breaker poster presentations, and 10 oral presentations.

Specifically:

  • Twenty-eight presentations on roxadustat for the treatment of anemia associated with CKD further demonstrated the depth and breadth of the roxadustat global Phase 3 development program and build on the known clinical profile of roxadustat in treating a broad spectrum of CKD patients.
  • Twelve presentations on CKD anemia epidemiology and disease state outlined the burden of anemia on CKD patients and their unmet medical need for innovative therapies.
  • Two late-breaking poster presentations explored associations between cardiovascular safety and hemoglobin levels achieved with roxadustat in both non-dialysis-dependent (NDD) and dialysis-dependent (DD) CKD patients.

Tuba: What are the knock-on effects of the newly released roxadustat data?

Peony Yu: The roxadustat clinical data at ASN Kidney Week 2020 Reimagined demonstrated consistent efficacy and reassuring safety results across the continuum of chronic kidney disease patients with anemia, adding to the established body of evidence highlighting roxadustat as a potential foundational treatment for this condition affecting millions of patients.

Roxadustat, being the first oral medicine for the treatment of CKD anemia which can be administered in patients’ homes, is conducive for telehealth as patients no longer need to receive treatment via injections in doctors’ offices or hospital infusion centers.

Tuba: Can you quickly recall your collaboration with AstraZeneca & Astellas for roxadustat?

Peony Yu: AstraZeneca and FibroGen are collaborating on the development and commercialization of roxadustat for the treatment of anemia in the U.S., China, and other markets in the Americas and in Australia/New Zealand, as well as Southeast Asia.

Astellas and FibroGen are collaborating on the development and commercialization of roxadustat for the treatment of anemia in territories including Japan, Europe, the Commonwealth of Independent States, the Middle East, and South Africa.

Tuba: Can you highlight the expansion of the clinical development of roxadustat in CKD & other indications?

Peony Yu: The roxadustat NDA for the treatment of anemia in CKD in patients on dialysis and those not on dialysis is under review by the U.S. Food and Drug Administration with a Prescription Drug User Fee Act date of December 20, 2020. Roxadustat is also in Phase 3 clinical development for anemia associated with myelodysplastic syndromes (MDS) and Phase 2 clinical development for chemotherapy-induced anemia (CIA).

Roxadustat is approved in China for the treatment of anemia in adult patients with CKD, both on dialysis and not on dialysis. In Japan, roxadustat is approved for the treatment of anemia in CKD patients on dialysis, and a supplemental NDA for the treatment of anemia in CKD patients not on dialysis is under regulatory review.

The marketing authorization application (MAA) of roxadustat for treatment of CKD in Europe is under review by the EMA. Similarly, the roxadustat NDA has been submitted to a number of countries, including Australia, Singapore, Canada, Mexico, Colombia, South Korea, India, Philippines, etc. Our goal for roxadustat is to serve patients around the world.

Source: Fibrogen

Tuba: As anticipated PDUFA date is December 20, 2020, if approved, how it will be helpful for the patients in the US?

Peony Yu: With roxadustat, FibroGen is advancing toward a new standard of care for anemia – an area that has not seen significant progress or the introduction of a new approach in 30 years. Patients are searching for new, convenient, and effective treatment options. If approved, roxadustat will be administered orally, mostly at home, eliminating the risks associated with needle injection and infection exposure with health care facilities and offering the potential for patients to live a more normal life.

Tuba: What are other products in FibroGen’s pipeline and discuss about their targeted indications?

Peony Yu: Pamrevlumab is a first-in-class antibody developed by FibroGen that inhibits the activity of connective tissue growth factor (CTGF), a common factor in fibrotic and proliferative disorders. Pamrevlumab is in clinical development for the treatment of idiopathic pulmonary fibrosis (IPF), locally advanced unresectable pancreatic cancer (LAPC), Duchenne muscular dystrophy (DMD), and coronavirus (COVID-19).

Notably, the U.S. FDA has granted Orphan Drug Designation to pamrevlumab for the treatment of patients with IPF, LAPC, and DMD. Pamrevlumab has also received Fast Track designation from the FDA for the treatment of patients with IPF and LAPC. These designations speak to the need for new, safe, and effective treatment options for these serious conditions.

Tuba: Can you provide an overview on the epidemiology of anemia associated with CKD?

Peony Yu: Anemia, a serious medical condition in which patients have insufficient red blood cells and low levels of hemoglobin and thus reduced oxygen delivery to the cells in the body, is a common early complication of CKD, affecting approximately 20% of CKD patients. CKD is estimated to occur in approximately 10-12% of adults worldwide and is predicted to become the fifth most common cause of premature death globally by 2040.

Source: Fibrogen

Tuba: Are FibroGen and partners planning to involve in any digital health solution to promote awareness of kidney diseases?

Peony Yu: We do believe digital health technology is a useful tool for promoting disease awareness, patient education, and treatment for patients and health care providers.  Our partner AstraZeneca has already started digital applications towards disease awareness of CKD anemia. 

Tuba: What next, we can expect from FibroGen to treat chronic and life-threatening conditions?

Peony Yu: FibroGen is pursuing groundbreaking research and science to drive forward a pipeline that may transform the patient experience and create new standards of care in anemia and an array of serious fibrotic conditions.

The company is currently developing roxadustat and continuing clinical development for pamrevlumab.

Tuba: What is FibroGen thinking about the potential benefits of using telehealth and mobile-based health resources to improve care for people with CKD?

Peony Yu: Roxadustat, being the first oral medicine for the treatment of CKD anemia which can be administered in patients’ homes, is conducive for telehealth as patients no longer need to receive treatment via injections in doctors’ offices or hospital infusion centers. There are many potential applications of digital health resources to improve anemia care in CKD patients.

About Peony Yu:

Dr. Peony Yu is Chief Medical Officer of FibroGen and has joined the company in 2008. She oversees all global and regional clinical development strategies and execution of the various clinical programs, as well as providing leadership for the roxadustat program.

Related Post: ViewPoints Interview: AstraZeneca’s Global Medicine Leader John Houghton Shares Insights on Roxadustat in Treating Patients with Anemia Due to CKD at ASN 2019

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ViewPoints Interview: Caris Life Sciences’ Dr. Spetzler Shares Insight on AI-Powered Clinico-Genomic Data Platform

In a recent interview with PharmaShots, Dr. Spetzler, President and Chief Scientific Officer of Caris Life Sciences shared his insights and highlights on data of the launch of CODEai.

Shots:

  • CODEai is a real-world clinico-genomic data platform that integrates Caris Life Sciences’ extensive catalog of molecular data with cancer treatment information and clinical outcomes data for ~215,000 patients covering over one million data points per patient
  • CODEai provides accurate data visualization and advanced predictive analytics to deliver clinicians, researchers, and scientists with personalized and precise cancer insights that can lead to a better understanding of how different cancers respond to treatments
  • Caris is also advancing precision medicine with Caris MAI (Molecular Artificial Intelligence) that combines its innovative service offerings, Caris Molecular Intelligence with its proprietary AI analytics engine, DEAN, to analyze the whole exome, whole transcriptome, and elements of the cancer proteomes

Tuba: Explain briefly about the web based CODEai platform and how does it bring the most out of it?

Spetzler: CODEai is a real-world clinico-genomic data platform powered by Artificial Intelligence. CODEai integrates Caris Life Sciences’ extensive catalog of molecular data with cancer treatment information and clinical outcomes data for over 215,000 patients covering over one million data points per patient.

CODEai is unlike any other real-world cancer data tool. It contains the largest set of integrated molecular and clinical outcomes data in the industry and its ease of use is unparalleled. Caris has the most comprehensive molecular profile on the market and CODEai leverages this extensive genomic, transcriptomic and proteomic information and matches it with clinical outcomes to take data and transform it to provide never-before-seen insights into the treatment of cancer by molecular composition. 

Tuba: What makes you motivated and interested to work and develop products in precision medicine and AI?

Source: Data Analytics

Spetzler: Patients are at the center of everything we do at Caris, and our company was founded with a simple but powerful purpose – to help improve the lives of as many people as possible. Progress in precision medicine continues to enhance our understanding of cancer and how to best treat it. It allows physicians to develop personalized treatment plans for their patients that utilize the most effective therapies available to them, potentially improving survival results.

Tuba: How does CODEai help clinicians, researchers, and scientists to understand the unique mechanism of cancer?

Spetzler: Integrating Caris’ database of profiled patient cases with associated treatments and outcomes, CODEai allows for customized cohort analysis based on a variety of search queries that include our industry-leading molecular profiling results, demographic data, diagnostic data and treatment and survival data. CODEai provides accurate data visualization and advanced predictive analytics to deliver clinicians, researchers and scientists with personalized and precise cancer insights that can lead to better understanding of how different cancers respond to treatments.

Tuba: What is the significance of AI in the development of Real-World Clinico-Genomic Data Platform?

Spetzler: Human-machine collaboration provides the most comprehensive analysis available today to characterize a patient’s tumor and support treatment decisions. The complexity of the system is too great for humans to decipher alone, and with AI and machine learning systems, vast amounts of clinical data can be analyzed using custom cohorts defined by clinicians, enabling the identification of new molecular subtypes of patients that benefit from customized treatment strategies.

Tuba: Can we have a brief discussion over Precision Oncology Alliance?

Spetzler: The Caris Precision Oncology Alliance (POA) is a growing collaborative network of leading cancer centers that demonstrate a commitment to precision medicine. These centers work together to advance comprehensive cancer profiling and establish standards of care for molecular testing in oncology through research focused on predictive and prognostic markers that advance the clinical outcomes of patients with cancer. Through the POA, Caris partners with top-tier cancer center across the country to leverage cutting-edge cancer research and therapeutic developments for the benefit of all patients with cancer. CODEai is available to members of the POA and offers our member institutions and investigators a unique tool that allows them to collaborate and share data to further advance breakthroughs in cancer research and treatment.

Tuba: What are the roles of POA members in advancing the delivery of molecular testing and raising the standards of care for profiling solid tumors?

Spetzler: The POA consists of leading cancer centers around the world that are committed to precision medicine and work collaboratively to advance the delivery of molecular testing and establish standards of care for profiling solid tumors.  It is the researchers at these centers that are driving the analysis to decipher the perturbations in each patient’s cancer to better understand and treat their disease.

Tuba: Clinico-Genomic data is set to pave the way for smarter and more precise therapies for cancer patients worldwide. Comment over the statement.

Spetzler: AI and machine learning are rapidly transforming the ability to analyze large amounts of molecular and clinical outcome data to provide unique insights into the genetic makeup and treatment of cancer by molecular composition, allowing physicians and researchers, for the first time, to truly decode cancer and improve patient’s lives.

Source: Caris LifeScience

Tuba: What are Caris’ other offerings that aid in advancing precision medicines?

Spetzler: The company’s suite of market-leading molecular profiling offerings assesses DNA, RNA, and proteins to reveal a molecular blueprint that helps physicians and cancer patients make more precise and personalized treatment decisions. MI Exome whole-exome sequencing with 22,000 DNA genes and MI Transcriptome whole transcriptome sequencing with 61,000 RNA transcripts along with cancer-related pathogens, bacteria, viruses, and fungi analysis run on every patient provides the most comprehensive and clinically relevant DNA and RNA profiling available on the market.

Caris is also advancing precision medicine with Caris MAI (Molecular Artificial Intelligence) that combines its innovative service offerings, Caris Molecular Intelligence with its proprietary AI analytics engine, DEAN, to analyze the whole exome, whole transcriptome, and elements of the cancer proteome. This information, coupled with mature clinical outcomes on thousands of patients, provides unmatched molecular solutions for patients and physicians.

Caris Pharmatech is changing the paradigm and streamlines the clinical trial process by assisting biopharma companies with accessing research-ready oncology sites for clinical trials. With over 200 research sites within the Caris Pharmatech Just-In-Time (JIT) Oncology Network, biopharma companies can identify and enroll more patients, faster. Caris Pharmatech JIT Clinical Trial Solutions focus on rapid site activation and patient enrollment to streamline the drug development process. By implementing Caris’ JIT Trial-Matching System, Caris will automatically match patients to clinical trials and sites can be activated and eligible to enroll patients within one week.

Tuba: How does Caris’ CODEai have the edge over other real-world cancer data tools?

Spetzler: CODEai is unlike any other real-world cancer data tool. It contains the largest set of integrated molecular and clinical outcomes data in the industry, cancer treatment information, and clinical outcomes data for over 215,000 patients covering over one million data points per patient, and its ease of use is unparalleled. The tool delivers an unmatched resource for developing a more complete picture of the molecular mechanisms of cancer, which has a dramatic impact on research initiatives, product development objectives, clinical trial services, and target identification opportunities.

Tuba: Can we have a highlight on Caris’ product pipeline? What specific you want to share with our readers/subscribers?

Spetzler: Caris has been developing a blood-based circulating exome assay capable of measuring tens of thousands of biomarkers in the blood. This revolutionary technology shows incredible promise to help patients and doctors find, identify, and treat cancer earlier. The current state-of-the-art for blood-based profiling measures cfDNA, but that can only be found in about 60% of late-stage cancer patients, compared to the Caris approach, which has been successful in measuring biomarkers in all patients. In addition to the blood-based technologies, we continue to explore the use of RNA in precision medicine through the study of RNA-based predictors and RNA fusion analysis. Additionally, our proprietary and advanced AI platform uses the largest existing dataset of tumor profiling results, matched with clinical outcomes, to identify new cancer subtypes with specifically defined molecular signatures.

Tuba: Since 2008, what are the Caris advancements in reinventing cancer care?

Spetzler: Founded in 2008, Caris is on a mission to help patients, clinicians, researchers, and payors navigate, advance, and reinvent cancer care. Our unique combination of expertise, proprietary technologies, clinical testing capabilities, and an extensive library of clinical data enable us to advance precision medicine. Caris has helped to redefine how cancer is understood. In 2008, cancer was a disease of the organ, today there are now cancers defined by their biomarkers; for example, NTRK positive or MSI positives, rather than the organ they started from.

About Dr. Spetzler:

Dr. Spetzler is a President and Chief Scientific Officer of Caris Life Sciences and has joined the company in 2019. He leads the company’s clinical testing service and the development of proprietary technologies to aid in the creation of precision medicine strategies for individual cancer patients and noninvasive technologies to identify and predict early-stage cancer.

Related News: ViewPoints Interview: True Digital Surgery’s Aidan Foley Shares Insight on the Aesculap Aeos Robotic Digital Microscope

The post ViewPoints Interview: Caris Life Sciences’ Dr. Spetzler Shares Insight on AI-Powered Clinico-Genomic Data Platform first appeared on PharmaShots.

ViewPoints Interview: True Digital Surgery’s Aidan Foley Shares Insight on Aesculap Aeos Robotic Digital Microscope

In a recent interview with PharmaShots, Aidan Foley, Chairman and Chief Operating Officer of True Digital Surgery share his insights and highlights on data of Aesculap Aeos Robotic Digital Microscope.

Shots:

  • The robotic digital microscope enables surgeons to execute precision movements in neurosurgery, spine, and ear, nose, and throat operations, through a multi-axis robotic arm. The platform also offers potential improvements to safety and efficiency during surgeries as the heads-up display can be viewed while wearing PPE, which overcome the spread of COVID-19
  • The platform utilizes 3D digital visualization, state-of-the-art software, and augmentation capabilities which are unmatched by any competitor digital microscope platform. Its customizable image modes functionality and fluorescence backlighting enhance the precision needs that surgeons require for complex surgical procedures
  • Additionally, the Aesculap Aeos Robotic Digital Microscope is approved for use and available in the EU and further markets

Tuba:  Discuss in detail about the specification of Aesculap Aeos Robotic Digital Microscope.

Aidan:  The Aesculap Aeos Robotic Digital Microscope combines enhanced surgical visualization and precise robotic movement to provide neurosurgeons with stunning 3D views and a very efficient way of conducting surgery. It offers precision movements guided by the surgeon via a robotic multi-axis arm. The state-of-the-art software provides surgeons with customizable image modes and fluorescence illumination. (Note: DIR fluorescence technology is currently available in European Markets only, not in the U.S.). The Aesculap Aeos platform’s technology encompasses 3D details with outstanding depth-of-field and 10x optical zoom that delivers full resolution regardless of magnification level. As an exclusively digital microscope platform, the Aesculap Aeos can be customized with simple software updates.

Approximately four-out-of-five neurosurgeons report pain after a day of surgery, in part owing to conventional microscope technology that requires contorting their body in unergonomic postures for many hours. These unergonomic positions often lead to debilitating pain which has been found to affect the performance of surgeons.  

Source: TDS

Tuba:  How is the Robotic Digital Microscope superior from the other competitor digital microscope platforms?

Aidan:  With the Aesculap Aeos, the surgeon can see both the fluorescent signal as well as the wide field of view, which is an advantage because they can operate in an environment that’s closer to what they’re used to looking at, but then also have context about the entire surgical scene while still getting the critical information they need about the tumor or blood flow. Robotic-assisted features that include location presets called WayPoints allow automated camera relocation to and from preset locations. The Lock-to-Target feature enables manual adjustment of the microscope position while maintaining focus on a surgical point of interest. Additionally, with coaxial illumination, light travels down the path the surgeon is looking down and eliminates shadows on the scene. The HDR (high-dynamic range) technology dramatically reduces the glint or glare that a surgeon sees reflecting off their tools or other shiny objects throughout a surgery.

Tuba:  Tell us more about the Image Modes feature of the Aesculap Aeos Robotic Digital Microscope.

Aidan:  The innovative Image Modes feature delivers augmentation capabilities without the need for an overlay and enables surgeons to view features in 3D that the human eye cannot, including the ability to manipulate color and the image in a way that’s beneficial for the surgeon. Additionally, the customizable fluorescence illumination enhances the patient’s micro-anatomy to provide precise information needed in complex procedures.

Tuba:  How is the digital microscope helping doctors amid the COVID-19 pandemic?

Aidan:  Healthcare professionals were already facing many challenges for their time and attention prior to the COVID-19 pandemic. By offering improved ergonomics and an immersive 3D 4K display, not available with traditional ocular microscopes, the Aesculap Aeos platform allows surgeons to perform surgery with their head raised seeing the microsurgical image on the 3D, 4K monitor while wearing a protective face shield – potentially leading to improved workplace health and safety for all the healthcare workers in the operating room during complex multi-hour microsurgical procedures.

Tuba:  What is your take on the efficiency and accuracy of a 3D surgery digital platform compared to the conventional methods?

Aidan:  The Aesculap Aeos can provide a solution to the limitations of traditional optical surgical microscopes, which can prolong surgery time and may contribute to patient safety issues such as tissue damage and skin burns owing to the heat generated through xenon illumination. The Aesculap Aeos uses cool LED illumination, making for a safer experience for the surgeon and patient. The 3D display, which isn’t available with traditional ocular microscopes, allows surgeons to perform surgery with their head raised seeing the microsurgical image on the 4K monitor, therefore minimizing physical strain. The Aeos can also be programmed to move very finely using digital controls.

Tuba:  Can we have a brief discussion over the collaboration of True Digital Surgery and Aesculap?

Aidan:  The Aesculap Aeos Robotic Digital Microscope is a result of True Digital Surgery’s cooperation with B. Braun’s Aesculap unit, a German-based company with a 150-year legacy in developing, manufacturing, and marketing innovative medical products and services to the healthcare industry. Together, the two companies’ expertise and experience have led us to develop a digital microscope which has proven to produce outstanding results with its recent sales successes against large surgical microscope players.

Tuba:  Can we expect more partnerships in the future considering it a successful one with Aesculap?

Aidan:  With a nearly 20-year record of creating new technologies that are designed to meet the precision needs of surgeons today, we are proud to be a disruptive force in the rapidly evolving MedTech sector. True Digital Surgery is actively developing features that will integrate artificial intelligence (AI), augmented reality (AR), and machine learning (ML) into upcoming digital microscopy products and we remain focused on collaborating with strategic partners.

Tuba:  Would you agree that integration of optics and robotics with AR can result in more innovative products beneficial to surgeons and patients?

Aidan:  Absolutely. True Digital Surgery is continuing the legacy of building a digital surgery platform with integrated applications and robotics to enhance the surgical experience and advance patient results. We have developed a 3D image system that vastly enhances what surgeons can see, and have integrated these capabilities with precision robotics and state-of-the-art algorithms that meet the needs of the modern O.R.

Tuba:  When we can expect its launch in other countries apart from the US?

Aidan:  In addition to the U.S., the Aesculap Aeos Robotic Digital Microscope is also approved for use and available in the European Union and additional global markets.

About Aidan Foley:

Aidan Foley is a Chief Executive Officer of True Digital Surgery (TDS) and also serves as its Chairman of the Board. He served multiple companies in the past and brings decades of executive-level experience from the Technology and Med Tech sectors to TDS

Related Post: ViewPoints Interview: Neurocrine’s Dr. Eiry Roberts Shares Insight on Ongentys (opicapone)

The post ViewPoints Interview: True Digital Surgery’s Aidan Foley Shares Insight on Aesculap Aeos Robotic Digital Microscope first appeared on PharmaShots.

ViewPoints Article: Organs on a chip (OOCs) – Transforming Animal Testing

Clinical studies cost money, time, and animal lives. There is an urgent need for alternative ways to model human diseases in-vitro to speed-up the new drug development process. Recently, Indian researchers have started exploring advanced technologies to replace animals in research. Organs on a chip (OOCs) is a novel concept, emerging as the next wave of 3D-culture models that function like a natural whole living organ. It would have the same biological activities, mechanical properties, and biochemical functions. The concept of “organ-on-a-chip”, also known as microfluidic in vitro cell culture systems was first established in 2010. The OOC market size is expected to reach $170 million by 2023, registering a CAGR of 63.2% from 2017 to 2023. The heart-on-chip type has a higher potential for growth in the global market. 

These microdevices can recapitulate the microscopic structure and functions of living human organs, including lung, intestine, kidney, skin, bone marrow, and blood-brain barrier, among others. OOCs are living, 3D cross-sections of major functional units of living organs. They are translucent and thus could provide an understanding of the inner functioning of human cells in living tissues. The recapitulations of cellular events in OOC devices provide them an edge over two‐dimensional (2D) and three‐dimensional (3D) cultures and open a gateway for their newer applications in biomedicine.

Source: ElveFlow

Classification of OOCs Based on their Working Mechanisms

  1. Membrane-based penetration and mechanical stimuli – These include Lung, kidney, heart, gut, blood-brain barrier on a chip
  2. Organ function mimicking based on anatomy – spleen and blood vessels on-chip are some of the examples.
  3. Perfusion-based OOC devices – brain, liver, womb on chip

Applications

  • Biological mechanism studies
  • Drug discovery and toxicity tests
  • Models for disease and cancer
  • Regenerative medicine
  • Radiobiology
  • Virus related: Viral-host interactions, viral therapy-resistance evolution, developing new antivirals, and understanding viral pathogenesis

Top Impacting Factors

The surge in applications of OOC devices in the pharmaceutical sector is multifactorial. Firstly, rising demand for OOCs i.e. in-vitro analysis of biochemical, and genetic & metabolic activities of living cells in a functional tissue. Secondly, drug screening involves drug toxicity or drug effectiveness in various organs. Lastly, the rise in demand for lung- & kidney-based organ culture devices involving laboratory-engineered and functional organs.

The advantages of OOC in pharmaceutical drug discovery are attributed to low cost, drug target identification, toxicity and drug efficacy evaluation, drug screening, the response of a combination, pharmacokinetics, and pharmacodynamics invitro.

As a better alternative to conventional cell culture and animal models, OOCs could really transform drug research and development. Broad applications of OOCs show promise but have certain limitations including their limited use in chronic diseases, adaptive immune response, metabolism, and complex systems such as endocrine, skeletal, and nervous system. Despite their limitations, OOCs have the potential to play a transformative role in the pharmaceutical industry and would streamline the preclinical process.

Conclusion

In a nutshell, it is concluded that Organ on a Chip (OOC) technology has exciting avenues to explore in drug discovery and development. These are the upcoming alternatives to traditional animal testing. More evidence is needed for OOCs, but progress will come from better investment and guidance from regulators. Therefore, it is essential to establish centers of excellence for developing such technologies that can replace animal testing and speed-up the drug development process.

References:

  1. Vaidyanathan G. India pushes for alternatives to animals in biomedical research. Nature. 2019 Oct 1;574(7776):16-7.
  2. Wu Q, Liu J, Wang X, Feng L, Wu J, Zhu X, Wen W, Gong X. Organ-on-a-chip: recent breakthroughs and future prospects. BioMedical Engineering OnLine. 2020 Dec 1;19(1):9.
  3. Yang JW, Shen YC, Lin KC, Cheng SJ, Chen SL, Chen CY, Kumar PV, Lin SF, Lu HE, Chen GY. Organ-on-a-Chip: Opportunities for Assessing the Toxicity of Particulate Matter. Frontiers in Bioengineering and Biotechnology. 2020 May 29;8:519..
  4. Organ-on-a-chip: the next generation platform for risk assessment of radiobiology
  5. Cells and Organs on Chip—A Revolutionary Platform for Biomedicine
  6. Tang H, Abouleila Y, Si L, Ortega-Prieto AM, Mummery CL, Ingber DE, Mashaghi A. Human organs-on-chips for virology. Trends in Microbiology. 2020 Jul 13.
  7. Organ-on-a-Chip, Tissue-on-a-Chip & Organoids Europe 2020
  8. Organ-On-Chip Market Overview

About Co-Author:

Dr. Sunaina Anand

Dr. Sunaina Anand, Pharm. D is a Clinical Pharmacist. She currently serves as Medical Affairs Executive in IntelliMed Healthcare Solutions. She previously interned in Tata Memorial Hospital and Columbia Asia Hospital, Bengaluru.

Related Post: ViewPoints Article: Digital Healthcare in India – Current Trends & Future

The post ViewPoints Article: Organs on a chip (OOCs) – Transforming Animal Testing first appeared on PharmaShots.

ViewPoints Interview: Neurocrine’s Dr. Eiry Roberts Shares Insight on Ongentys (opicapone)

In a recent interview with PharmaShots, Dr. Eiry Roberts, Chief Medical Officer of Neurocrine Biosciences shares his insights and highlights on data of Ongentys.

Shots:

  • In a post-hoc, sub-group analysis of the P-III BIPARK-1 study demonstrated greater reductions in overnight “off” time and time to morning “on” time compared to entacapone in patients with PD with motor fluctuations
  • The new P-III post-hoc sub-group analysis demonstrated that long-term treatment with Ongentys when used as an add-on therapy reduced “On” time with troublesome dyskinesia and increased good “On” time without troublesome dyskinesia in patients with PD with motor fluctuations
  • Long term use of therapy leads to a reduction in the patient’s average daily levodopa dosage requirement. Ongentys (qd, PO) is a selective and reversible COMT inhibitor and has received the US FDA’s approval as an add-on treatment to levodopa/carbidopa in patients with PD experiencing “off” episodes

Tuba: We understand that six abstracts of ONGENTYS were presented during ANA 2020. Can we have a quick highlight for our readers of all the presentations/ abstracts?

Eiry:  The data that Neurocrine Biosciences presented in collaboration with BIAL at the ANA 2020 Virtual Meeting provide further insight on how adding once-daily ONGENTYS® (opicapone) capsules to levodopa/carbidopa therapy, the gold standard for treatment of motor symptoms, can help patients with Parkinson’s disease better manage disruptive motor fluctuations over the course of the day. Highlights include:

  • Data from two post-hoc, sub-group analyses of Phase III data showed that patients treated with ONGENTYS saw greater reductions in overnight “off” time and time to morning “on” time compared to entacapone in patients with Parkinson’s disease with motor fluctuations. A third post-hoc analysis showed that ONGENTYS led to a greater increase in the portion of patients who woke up on in “on” status from first-morning levodopa intake.
  • In a separate Phase III post-hoc sub-group analysis, long-term use of ONGENTYS in patients with Parkinson’s disease with motor fluctuations reduced “on” time with troublesome dyskinesia and increased good “on” time without troublesome dyskinesia.

Tuba: Is Neurocrine planning to evaluate the potential of ONGENTYS in other Neurological Diseases?

Eiry:  Neurocrine does not plan to evaluate ONGENTYS in other neurological diseases at this time.

Neurocrine Biosciences is building a world-class, neuroscience-focused pipeline with candidates to address a variety of serious and underserved neurology, neuroendocrinology, and psychiatry conditions with a high unmet need, including Parkinson’s disease

Tuba: Does the company have any other pipeline or marketed products targeting PD?

Eiry:  Neurocrine Biosciences is building a world-class, neuroscience-focused pipeline with candidates to address a variety of serious and underserved neurology, neuroendocrinology, and psychiatry conditions with a high unmet need, including Parkinson’s disease.

Neurocrine Biosciences is developing NBIb-1817 (VY-AADC) for the treatment of Parkinson’s disease with Voyager Therapeutics as part of a strategic collaboration announced in January 2019. NBIb-1817 is an investigational gene therapy designed to restore AADC enzyme activity in brain cells where it can convert levodopa to dopamine. Small open-label studies performed with NBIb-1817 have shown that a single administration of the NBIb-1817 gene therapy can provide clinically meaningful improvements in motor function in patients with Parkinson’s disease. These studies also demonstrated that one-time treatment with investigational NBIb-1817 could lead to an increase in activity of the AADC enzyme measured by positron emission tomography (PET).  Our hope is that NBIb-1817 will help patients experience less “off” time and more “on” time and improve motor symptom control.

NBIb-1817 has the potential to add to the armamentarium of treatment options for patients with Parkinson’s disease and could be complementary to oral therapies, such as ONGENTYS. Clinical studies to support the registration of NBIb-1817 are ongoing with a new pivotal study, RESTORE 2, currently planned to start in 2021. 

Tuba: The Phase III Clinical Studies (BIPARK-1 and BIPARK-2) supports its efficacy in adults with Parkinson’s disease (PD) who are having “OFF” episodes. Is there any study evaluating its efficacy in children and pregnant ladies?

Eiry:  We do not have plans to evaluate ONGENTYS for children and pregnant women at this time. Of note, most people with Parkinson’s disease are diagnosed in their 60’s.  

Tuba: In collaboration with BIAL, you have targeted multiple countries, including the US, EU, and Canada. What are the other geographies you are focusing on?

Eiry:  Neurocrine Biosciences received FDA approval of ONGENTYS in April 2020. We are pleased to bring this important new treatment option to the Parkinson’s community. We are committed to ensuring that all patients with Parkinson’s disease who might benefit from ONGENTYS have access to it in the U.S.

Tuba: How Neurocrine’s INBRACE Support Program aid patients living with movement disorders?

Eiry:  The INBRACE® Support Program is designed to help patients who are prescribed ONGENTYS, from prescription fulfillment to navigating coverage requirements and providing financial assistance information to support patients along their treatment journey.

Source: Parkinson’s NSW

Tuba: What should be the next steps in terms of research or development in Parkinson’s disease?

Eiry:  There remains a significant unmet need for new treatment options that optimize motor symptom control in patients with Parkinson’s disease. The standard of care for advanced Parkinson’s disease has not significantly changed in decades, and it is our hope that NBIb-1817 has the potential to become the first approved gene therapy for Parkinson’s disease.

Tuba: What Neurocrine thinks about digital health technologies could be used to improve PD care?

Eiry:  Parkinson’s care may be improved by new advances in digital technologies. Digital devices that provide personalized information on health measures collected during patients’ daily life activities could be useful to patients and their health care providers for monitoring of Parkinson’s disease manifestations beyond standard in-office visits.

Tuba: Is there any digital tool the company is working on that helps in understanding the daily Parkinson’s experience?

Eiry:  As part of our ongoing commitment to improve the lives of patients living with movement disorders, including Parkinson’s disease, we are looking into ways to help improve care for patients with Parkinson’s disease, including digital technologies. 

Tuba: Would you like to note any additional takeaways on the ONGENTYS?

Eiry:  ONGENTYS was recently approved by the U.S. Food and Drug Administration (FDA) as the first and only once-daily catechol-O-methyltransferase (COMT) inhibitor as an add-on to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes. The availability of ONGENTYS offers hope to patients by significantly decreasing “off” time and increasing “on” time without troublesome dyskinesia, which helps lead to more consistent motor symptom control, presenting an exciting new option for patients. The data we shared at the 2020 ANA Virtual Conference reinforces why it may be valuable to add once a day ONGENTYS to a patient’s treatment regimen as early as possible.

About Dr. Eiry Roberts:

ViewPoints Interview: Neurocrine’s Dr. Eiry Roberts Shares Insight on ONGENTYS (opicapone)

Ms. Eiry Wyn Roberts was appointed as Chief Medical Officer in January 2018 and is responsible for all clinical development and medical affairs activities at Neurocrine Biosciences. Dr. Roberts has over 25 years of research and development experience in the pharmaceutical industry across all phases of drug development from research through commercialization in multiple therapeutic areas, including neuroscience, inflammation, oncology and metabolic diseases.

Related Post: ViewPoints Interview: Dicerna’s Doug Fambrough Shares Insight on Nedosiran Data Presented at ASN Week 2020

The post ViewPoints Interview: Neurocrine’s Dr. Eiry Roberts Shares Insight on Ongentys (opicapone) first appeared on PharmaShots.

ViewPoints Interview: Dicerna’s Doug Fambrough Shares Insight on Nedosiran Data Presented at ASN Week 2020

In a recent interview with PharmaShots, Doug Fambrough, Ph.D., President and CEO of Dicerna shares his insights and highlights on data of Nedosiran presented at ASN Week 2020.

Shots:

  • All participants regardless of PH subtype, achieved normal or near-normal Uox excretion @day180, 92% participants (100% & 67% with PH1 & PH2) achieved normal Uox excretion at one or more visits, 62% participants (70% & 33% with PH1 & PH2) demonstrated normalized Uox excretions on at least three consecutive visits, maximum reduction in Uox excretion (70.9%)
  • Trial timelines were updated in August with enrollment completion for the pivotal PHYOX2 trial by year-end 2020, which should set up Dicerna for an NDA submission in the Q3’2021
  • Dicerna is currently looking for partners to commercialize Nedosiran outside the US. Nedosiran is an investigational candidate in development for the treatment of all three known types of PH – PH1, PH2, and PH3, act by inhibiting the LDH enzyme

Tuba:  Can we have the highlights of your presentation at ASN Week 2020 in a non-scientific way?

Doug: Primary hyperoxaluria (PH) is a family of rare genetic disorders causing hepatic oxalate overproduction that can result in life-threatening kidney damage. In PH, excess oxalate can lead to chronic kidney stones, progressive kidney damage including the possibility of end-stage renal disease, and systemic oxalosis. There are three known PH subtypes – PH1, PH2, and PH3 – and there is currently no available treatment approved for this rare disease.

At ASN Kidney Week 2020, we presented an interim analysis of safety and efficacy data from our ongoing long-term, open-label clinical study of Nedosiran (a study we call PHYOX™3), which is our lead investigational candidate in development for PH1, PH2, and PH3. A key PH measure is the oxalate excretion in urine (urinary oxalate), and we presented data on once-monthly dosing of Nedosiran in participants with PH1 and PH2 who had previously participated in our Phase 1 study and had reached Day 180 of the PHYOX3 trial:

  • All PH1 participants achieved normal urinary oxalate excretion at one or more timepoints by Day 180;
  • All PH2 participants achieved normal or near-normal urinary oxalate excretion at one or more timepoints by Day 180;
  • Nedosiran was well tolerated, and no serious safety concerns were identified in this trial patient population.

Tuba:  Dicerna presented new interim data from PHYOX3 long-term, OLE study at ASN Kidney Week. When can we expect the complete results of nedosiran?

Doug:  We are evaluating Nedosiran in the PHYOX development program, which includes multiple clinical studies of all three known PH subtypes – PH1, PH2, and PH3. The PHYOX3 trial is a long-term, open-label study into which any participant previously completing a PHYOX trial may enroll, as well as their siblings with PH who are between the ages of six and 18. Another important trial in our PHYOX program is our pivotal PHYOX2 trial, for which we are targeting enrollment completion by the end of 2020 and trial completion in the first half of 2021, which would position us to submit a New Drug Application next year.

Tuba:  Discuss in detail about the complete PHYOX clinical program?

Doug:  The PHYOX program comprises multiple trials inclusive of the three known subtypes of PH, adults and adolescents, and patients with varying renal status. The following is a high-level summary of PHYOX clinical trials:

  • PHYOX1 was a Phase 1 safety and efficacy study of Nedosiran in participants with PH1 or PH2; this study is complete.
  • PHYOX2 is our ongoing double-blind, randomized, placebo-controlled pivotal trial.
  • PHYOX3 is the aforementioned ongoing open-label trial evaluating the long-term safety and efficacy of Nedosiran.
  • PHYOX4 is a double-blind, randomized, placebo-controlled trial in participants with PH3.
  • PHYOX7 is a multidose trial in participants (birth to adult) with PH and end-stage renal disease (ESRD).
  • PHYOX8 is an open-label study to evaluate the safety and efficacy of Nedosiran in children 0-5 years old with PH.
  • PHYOX-OBX is a natural history study to evaluate the association between urinary oxalate excretion and kidney stone formation rate in PH3, the least researched and least understood the type of PH.

Tuba:  Are the plans for NDA submission on track? Was there any impact of COVID-19 pandemic or any other factor on the regulatory submission?

Doug:  Early in the pandemic, we, like many others, took steps in an effort to ensure business and clinical trial continuity during what was a highly fluid and unprecedented time. For the PHYOX program, we were able to transition certain site visits to a combination of at-home nurse visits with investigator telehealth assessments for dose administration and safety follow-up, enabling our development program to continue, albeit at a slightly slower pace. We were able to update our trial timelines in August and have guided to enrollment completion for the pivotal PHYOX2 trial by year-end 2020, which should set up us for an NDA submission in the third quarter of 2021.

Tuba:  Which countries would be mainly targeted for nedosiran’s approval?

Doug:  We are seeking to have nedosiran approved and available globally.

Tuba:  Can we have a discussion on ultra-rare Primary Hyperoxaluria (PH) and its epidemiology?

Doug:  Using genetic studies, we believe PH is more common than previously realized. It is estimated that approximately 2,700 people in the U.S. have PH1, 1,700 have PH2 and approximately 4,100 have PH3, while diagnosis rates are estimated to be ~40-50%, ~10%, and ~7%, respectively. Epidemiology data suggest that there are similar numbers of patients in Europe. There is less data about PH in other parts of the world, but it’s likely that the disease occurs in all populations. As the first described subtype, PH1 is the most well-known and understood of the three, yet all PH subtypes are likely underdiagnosed.

Tuba:  Are you planning for any collaborations for the commercialization of nedosiran globally as we are aware that Dicerna collaborated with multiple global companies including Roche, Eli Lilly?

Doug:  Our current plan for nedosiran is to commercialize it in the U.S. ourselves, and we are currently in discussions with potential partners to commercialize nedosiran outside the U.S.

Tuba:  Tell us briefly about the GalXC RNAi technology platform. Also, for exploring its potentials, Dicerna collaborated with multiple companies, give a brief note on your collaborations?

Doug:  Our proprietary GalXC technology leverages a naturally occurring biologic process, ribonucleic acid interference, or RNAi, to create therapies that silence disease-causing genes. Our powerful platform enables us to develop highly selective and specific RNAi compounds that have a unique configuration known as a tetraloop. This configuration interfaces effectively with the RNAi process and allows us to easily modify a compound’s chemical structure to maximize stability and potency. Our current GalXC RNAi technology is optimized to target liver diseases, and our scientists are further developing our technology to target diseases in other organ systems.

Our first collaboration was announced in November 2017 with Boehringer Ingelheim and focused on chronic liver diseases. Since then, we have established collaborations with Alexion to create RNAi therapies for complement-mediated diseases; Lilly for new medicines for cardiometabolic disease, neurodegeneration, and pain; Roche for chronic hepatitis B virus infection; and with Novo Nordisk for cardiometabolic diseases.

Tuba:  What are Dicerna’s further plans regarding nedosiran?

Doug:  We are committed to researching and developing therapies for all patients with PH regardless of subtype. We plan to submit an NDA to the FDA for nedosiran next year and intend to partner outside the U.S. with the goal of bringing this potential treatment to people living PH as quickly as possible.

About Doug Fambrough:

Douglas Fambrough co-founded Dicerna in 2007 and has served as the Company’s president and CEO since 2010. His background as both a genomic scientist and venture capitalist has been instrumental in the evolution of Dicerna, from the development of its unique GalXC platform to its transformation into a publicly-traded company.

Related Post: ViewPoints Interview: Eli Lilly’s Dr. Lotus Mallbris Shares Insights on Mirikizumab

The post ViewPoints Interview: Dicerna’s Doug Fambrough Shares Insight on Nedosiran Data Presented at ASN Week 2020 first appeared on PharmaShots.

ViewPoints Interview: Eli Lilly’s Dr. Lotus Mallbris Shares Insights on Mirikizumab

In a recent interview with PharmaShots, Dr. Lotus Mallbris, the Vice President of Immunology Development at Eli Lilly shares her insights and highlights on Mirikizumab. 

Shots:

  • @52wks. ~60% achieved endoscopic responses (58.5% in IV dosing group and 58.7% in the SC group) while 45% + achieved PRO remission (46.3% in the IV group and 45.6% in the SC group)
  • If approved for IBD indications, mirikizumab – a biologic entity that blocks the activity of the IL-23 cytokine – could be one of the first IL-23s approved for ulcerative colitis, a disease state with fewer biologic treatment options, as well as one of the first of this class to be approved for Crohn’s disease
  • Lilly is currently investigating mirikizumab in P-III clinical trials. Lilly expects topline results for the P-III induction data in UC in the spring of 2021 and for the P-III Crohn’s data in 2022.

Tuba: How was your virtual experience at UEG week? Can we have a quick highlight on the data of mirikizumab presented at UEG Week?

Lotus: I was very pleased with my experience at UEG Week; although the format was different than previous years considering the meeting was entirely virtual, it was a great opportunity to learn about the latest innovation in the gastroenterology space. Lilly had the opportunity to present new efficacy and safety data from the Phase 2 SERENITY study evaluating mirikizumab in patients with moderately to severely active Crohn’s disease at this year’s virtual UEG Week. These are the first 52-week data for mirikizumab in Crohn’s disease (CD) and the results continue to build upon the data already presented in ulcerative colitis (UC). These results are an important part of the clinical development program for mirikizumab, and Lilly hopes these data can provide optimism for those living with Crohn’s disease.

At 52 weeks, patients who showed endoscopic improvement at 12 weeks and continued treatment with mirikizumab achieved the following results:

  • Endoscopic response: Nearly 60% of patients achieved endoscopic response (58.5% in the randomized IV dosing group and 58.7% in the SC group).
  • Patient-Reported Outcomes (PRO) remission: More than 45% of patients achieved PRO remission (46.3% in the IV group and 45.6% in the SC group).

Among the subset of patients who achieved an endoscopic response at Week 12, 69.6% and 66.7% in the IV (n=23) and SC (n=24) groups, respectively, also had endoscopic response at Week 52. Additionally, among those with endoscopic remission at Week 12, 50.0% and 64.3% in the IV (n=6) and SC (n=14) groups, respectively, also had endoscopic remission at Week 52. These Phase 2 data support and reinforce the potential for mirikizumab in the ongoing, pivotal VIVID Phase 3 program as a potential treatment for patients with Crohn’s disease.

Tuba: What are the other treatments across Lilly’s immunology portfolio for transforming the treatment experience of patients with autoimmune diseases?

Lotus: We recognize there are still significant unmet needs, as well as personal and societal costs, for people living with autoimmune diseases and our goal is to minimize the burden of disease and help patients find treatments that offer meaningful improvements. Our immunology portfolio includes first in class or first in disease molecules and we’re investing in leading-edge clinical approaches across our deep pipeline, which also includes early candidates currently in Phase 1 and Phase 2 development. Through these treatments, we hope to one day offer therapeutic options for patients across ten disease areas:

  • Mirikizumab is an investigational treatment that is being studied for the treatment of adults with Crohn’s disease, ulcerative colitis and moderate to severe plaque psoriasis.
  • Taltz® (ixekizumab) is approved for moderate to severe plaque psoriasis in adults and children, as well as active psoriatic arthritis, active non-radiographic axial and active ankylosing spondylitis in adults.
  • Olumiant® (baricitinib) is indicated for adults with moderately to severely active rheumatoid arthritis, and is being studied for moderate to severe atopic dermatitis (AD); systemic lupus erythematosus (SLE), which received Fast Track designation from the Food and Drug Administration (FDA); and alopecia areata (AA), which received Breakthrough Therapy designation from the FDA earlier this year.
  • Lilly recently announced a positive CHMP opinion by the European Medicines Agency’s (EMA) for Olumiant in AD, and if approved, Olumiant could become the first oral JAK inhibitor available in the EU.
  • Lebrikizumab is a novel, investigational, a monoclonal antibody in Phase 3 studies to evaluate its safety and efficacy in adolescent and adult patients with moderate-to-severe atopic dermatitis.

Mirikizumab is an investigational treatment that is being studied for the treatment of adults with Crohn’s disease, ulcerative colitis and moderate to severe plaque psoriasis.

Tuba: Are there any specific population or any group in which mirikizumab shows its higher and lower efficacy & safety?

Lotus: In addition to IBD, mirikizumab is also being studied in adults with moderate to severe psoriasis. Earlier this year, Lilly presented results from the Phase 3 OASIS-2 study, which showed mirikizumab met the primary and all key secondary endpoints versus placebo at Week 16 (superiority), as well as all key secondary endpoints versus Cosentyx® (secukinumab) at Week 16 (non-inferiority) and Week 52, including superiority in skin clearance at Week 52.

In the data presented at UEGW, mirikizumab demonstrated efficacy in adults with Crohn’s disease over 52 weeks of treatment. Additional studies in adults are ongoing, and Lilly expects Phase 3 Crohn’s data in 2022.

Tuba: As Lilly is evaluating mirikizumab in three different indications i.e. psoriasis, UC & CD. Can we have a quick review on the clinical data related to the targeted disease?

Lotus: Mirikizumab is being studied for the treatment of immune diseases, including psoriasis, ulcerative colitis and Crohn’s disease:

  • In psoriasis, Lilly presented results in July 2020 from the Phase 3 OASIS-2 study, which showed mirikizumab met the primary and all key secondary endpoints versus placebo at Week 16 and all key secondary endpoints versus Cosentyx® (secukinumab) at Week 16 and Week 52, including superiority in skin clearance at Week 52.
  • In addition to the data presented at UEGW this year, Lilly also expects topline results for Phase 3 Crohn’s data in 2022, following positive endpoints being met at 12 weeks in its Phase 2 trial.
  • Lilly expects topline results for the Phase 3 induction data in ulcerative colitis in the spring of 2021.
Source: Pinterest

Tuba: As the market is flooded with multiple biologics in IBD, what is Lilly’s strategy to position its therapy in CD?

Lotus: Inflammatory bowel disease (IBD), which included Crohn’s disease and ulcerative colitis, affects more than 10 million people worldwide. Crohn’s disease is a serious and difficult-to-treat condition, and there is a significant need for additional treatments that can address the challenging and painful symptoms of people living with Crohn’s disease experience. In the study presented at UEG Week, patients treated with mirikizumab showed a response in both symptom relief and endoscopic response and remission at 52 weeks. Based on these Phase 2 data, we’re optimistic Lilly is one step closer to providing relief for patients. 

Tuba: AbbVie’s Skyrizi, Johnson & Johnson’s Tremfya and Allergan’s Brazikumab, and Novartis’ Cosentyx are some competitors of mirikizumab.  What are other potential threats to the therapy?

Lotus: Lilly does not comment on competitors or data/trials conducted by other companies.

Tuba: What are your major steps in the digital world to transform inflammatory bowel disease (IBD) care?

Lotus: Through key partnerships, we are investigating several different approaches to enhance patient care, including the use of wearable sensors to collect biometric data and help us understand how patients respond to medications. We’re also leveraging artificial intelligence to better diagnose certain GI issues. Lastly, we’re conducting research to determine how digital disease management tools can provide a better understanding of one’s condition, so patients can have better discussions with their healthcare professional.

Tuba: As you select HealthVoyager as a winner of the digital health innovation challenge for inflammatory bowel disease. Can you highlight the specification of the digital tool you are working on and when can we expect its availability?

Lotus: HealthVoyager, an application developed by Boston Children’s Hospital and Klick Health, was named the winner of Lilly’s 2019 digital health open innovation challenge. The idea leverages a highly customizable software platform for doctors to create a personalized and immersive educational experience for patients living with inflammatory bowel disease (IBD). We are confident in the application’s success and support the team in their pursuit of its development, as Lilly focuses on other priorities for people living with inflammatory bowel disease. For additional updates about HealthVoyager, please contact Sheryl Steinberg at Klick Health ([email protected]).

Tuba: How do you think mirikizumab will raise the standard of Lilly in the field of immunology?

Lotus: If approved for IBD indications, mirikizumab – a biologic entity that blocks the activity of the interleukin 23 (IL-23) cytokine – could be one of the first IL-23s approved for ulcerative colitis, a disease state with fewer biologic treatment options, as well as one of the first of this class to be approved for Crohn’s disease.

We are excited about the data presented at UEG Week and are encouraged by these Phase 2 results. We look forwarding to continuing our clinical program for mirikizumab, and hope it, along with our already robust pipeline in immunology, will help raise the standard of care for those living with Crohn’s disease.

Tuba: What would be the pricing of the mirikizumab to compete with the emerging threats of lower-priced biosimilars in the space?

Lotus: Lilly does not comment on future pricing strategy.

Tuba: When can we expect the availability of mirikizumab in the US & EU?

Lotus: We are currently investigating mirikizumab in Phase 3 clinical trials. Lilly expects topline results for the Phase 3 induction data in ulcerative colitis in the spring of 2021 and for the Phase 3 Crohn’s data in 2022.

About Dr. Lotus Mallbris:

Lotus Mallbris, M.D., Ph.D., is the Vice President and Global Head of Immunology Product Development at Eli Lilly. She has joined Lilly in 2015 and leads the company’s global clinical development and global medical affairs teams across the dermatology, rheumatology, and gastroenterology fields.

Related Post: ViewPoints Interview: Eli Lilly’s Dr. Lotus Mallbris Shares Insights on Baricitinib

The post ViewPoints Interview: Eli Lilly’s Dr. Lotus Mallbris Shares Insights on Mirikizumab first appeared on PharmaShots.

ViewPoints Interview: Takeda’s Andrea Stancati Shares Insights on Entyvio (vedolizumab) SC Formulation

In a recent interview with PharmaShots, Andrea Stancati, Vice President, Head GI Global Medical Franchise shares his insights and highlights of Entyvio (vedolizumab)

Shots:

  • The ongoing P-IIIb VISIBLE OLE study involves assessing of Entyvio (SC) in adult patients with UC or CD, following enrolment and participation in the VISIBLE 1 (UC) or VISIBLE 2 (CD) studies. Patients who completed the maintenance period up to 52wks. (randomized completers) or who achieved clinical response @14wks. (non-randomized 14wks. responders) after a third IV infusion @6wks. received Entyvio (SC, 108mg, q2w)
  • Interim analysis from the VISIBLE OLE study showed long-term findings consistent with the known safety profile of vedolizumab with maintained rates of clinical remission and corticosteroid-free clinical remission
  • Entyvio is the first maintenance biological therapy approved across the EU in both IV and SC formulations to treat moderately to severely active UC or CD. VISIBLE OLE results presented at UEG Week Virtual 2020 congress

Tuba:  Can we have a brief summary of Takeda’s presentation at the UEG Week Virtual 2020 congress?

Andrea: During the UEG Week Virtual 2020 congress, we presented interim results from the VISIBLE open-label extension study on the long-term safety and efficacy of maintenance treatment with the subcutaneous formulation of Entyvio® (vedolizumab) in patients with moderately to severely active ulcerative colitis. Following two years of maintenance therapy with subcutaneous vedolizumab, long-term safety findings were consistent with the known safety profile of vedolizumab.

Additionally, patients continued to demonstrate clinical benefit from treatment, through the maintenance of clinical remission and corticosteroid-free clinical remission rates. These latest safety and effectiveness results are important as they provide further evidence that the benefits received from treatment with subcutaneous vedolizumab are sustained during long-term maintenance therapy.

Tuba :  Please tell us more about the mechanism of Entyvio (vedolizumab) and its uniqueness?

Andrea:  Entyvio is a gut-selective biologic which is approved in both intravenous and subcutaneous formulations.  It is a humanized monoclonal antibody designed to specifically antagonize the alpha4beta7 integrin on the cell surface of circulating T lymphocytes, inhibiting the binding of alpha4beta7 integrin to intestinal mucosal addressin cell adhesion molecule 1 (MAdCAM-1) on the endothelial lining of capillaries. By blocking that interaction and inhibiting the alpha4beta7 integrin, Entyvio prevents T lymphocytes from going into the bowel wall and promoting and sustaining the cycle of inflammation that we see in patients with ulcerative colitis or Crohn’s disease.

Tuba: Is Takeda evaluating the safety & efficacy of Entyvio in pediatric patients with UC & CD?

Andrea:  Yes. While Entyvio is not currently approved for use in people under the age of 18, we have undertaken several phase 2 and 3 clinical studies to understand the potential use of Entyvio in pediatric patients.

Source: New York Presbyterian

Most recently, in May 2020, we completed a phase 2 study (NCT03138655) that evaluated the pharmacokinetics, safety, and tolerability of vedolizumab in patients aged 2-17 with moderately to severely active ulcerative colitis or Crohn’s disease. A phase 2b extension study (NCT03196427) is now in progress to determine the long-term safety profile of Entyvio, with results expected in 2021 and full completion in 2024. We recognize the considerable need to alleviate the debilitating symptoms experienced by children with inflammatory bowel disease and are working to optimize their care with new, targeted treatment solutions.

Tuba:  EU check, Canada check, Australia check, what are your plans for the geographic expansion of Entyvio (vedolizumab) SC formulation?

Andrea:  We intend to work with regulatory bodies globally to seek approval for the new subcutaneous formulation.

We are committed to providing physicians with treatment options that suit their patients’ individual needs and preferences, whether that is intravenous or subcutaneous for maintenance therapy. Some patients may prefer a subcutaneous formulation as it allows flexibility, while others may favor intravenous administration due to regular touchpoints with a healthcare professional in a medical setting.

Tuba:  Are there any new formulations of Entyvio that Takeda is experimenting with?

Andrea:  The recent approval of the subcutaneous formulation of Entyvio has been a significant step forward in advancing care, offering another treatment formulation to suit the individual medical needs, preferences, and different lifestyles of patients. The patient experience is very important to Takeda, and our next focus is on evolving patient care in inflammatory bowel disease with a needle-free Entyvio delivery device. We are working with Portal Instruments on the needle-free device, which is currently in development.

Entyvio is the only gut-selective biologic that addresses inflammation specifically in the gut, significantly differentiating from all other non-selective therapies

Tuba: How is Takeda’s Entyvio different from other competitors in this space?

Andrea:  Entyvio is the only gut-selective biologic that addresses inflammation specifically in the gut, significantly differentiating from all other non-selective therapies. It was the first maintenance biologic therapy approved across Europe in both intravenous and subcutaneous formulations to treat patients with moderately to severely active ulcerative colitis or Crohn’s disease. Entyvio is now approved in over 70 countries worldwide, with more than 510,000 patient-years of exposure to date, providing extensive knowledge on the treatment’s effectiveness and safety.

Tuba: As Takeda is committed to gastrointestinal innovation, what can we expect to see from Takeda to improve the QoL of patients with gastrointestinal diseases?

Andrea:  We’ve continued to demonstrate our patient-centric approach by further investigating and understanding the efficacy and safety profile of Entyvio. We have a number of important clinical studies still running, including in potential new patient populations, which will provide greater knowledge and enhance the body of evidence around the use of the therapy in inflammatory bowel disease. Furthermore, the newly approved subcutaneous formulation of Entyvio allows patients and healthcare professionals to better personalize care in line with which delivery method works best for the individual.

Longer-term, we are working with Portal Instruments on needle-free drug delivery options for patients who have problems with needles. These projects are a small part of our commitment to improving patient quality of life, aside from the research and development work we’re doing to bring new therapeutic options to patients.

Tuba: What is Takeda’s vision to restore the life of patients suffering from GI and liver diseases?

Andrea:  Patients are at the heart of our organization. At Takeda, we see no higher priority than closing the gap between the unmet needs and deserved solutions for those that battle these complicated conditions.

We believe that GI and liver diseases are not just life-disrupting conditions but diseases that can impact a patient’s quality of life. Routines are interrupted, symptom management takes precedence, and the emotional pain can be just as present as the physical. Beyond a fundamental need for effective treatment options, we understand that improving patients’ lives also depends on their needs being recognized. Our approach is a simple one: if there is a need, we will seek to meet it; if there is a patient, we will strive to find a viable treatment solution; if there are questions, we will search relentlessly for answers.

Tuba: Can we have a comment on your rich and diversified pipeline targeting gastrointestinal diseases?

Andrea:  We are committed to providing novel medicines for GI and liver diseases globally. Through specialized and strategic in-house development, external partnerships, in-licensing, and acquisitions, we currently have several promising early-stage assets in development. We remain committed to delivering innovative therapeutic options for patients with GI and liver diseases.

Our core research focus areas in gastroenterology are GI inflammation, GI motility, and advanced liver diseases. In particular, we are making significant strides toward closing the gap on new areas of unmet needs for patients who have celiac disease, eosinophilic esophagitis, alpha-1 antitrypsin-associated liver disease, Crohn’s disease, and acute pancreatitis, among others.

Our patient-centric philosophy begins with exploration as innovative as the treatments it leads to. To gain a greater understanding of the causes of GI and liver diseases, we collaborate with like-minded companies who are advancing the way patients are diagnosed and treated. One example of this is a new collaboration that has enabled us to obtain an intestine chip for research purposes that recreates the intestinal lining and maybe the “gateway” to new discoveries.

For more information on the Takeda pipeline, visit this link

Tuba: Is Takeda looking for any digital solutions for patients with IBD?

Andrea:  As part of our innovation in gastroenterology, we are exploring diverse ways to optimize the care and experiences of patients affected by inflammatory bowel disease. Our unique and holistic approach goes beyond providing patients with medicines by creating novel awareness campaigns and using medical education as a lever to empower patients. We believe that elevating gastrointestinal diseases starts with empathy. To make a real difference, we must understand how gastrointestinal diseases impact our patients’ everyday lives.

An example of this is the creation of Takeda’s digital disease awareness program called ‘In Their Shoes.’ This immersive, award-winning simulation is built around mobile technology. It has been highly successful at helping others, including healthcare professionals, gain more knowledge by experiencing what it’s like to live with inflammatory bowel disease and its complications. Over 2,000 participants from more than 30 countries worldwide have had the opportunity to simulate a patient’s daily life via mobile app challenges, experiencing first-hand the emotional and physical burden of living with inflammatory bowel disease.

About Andrea Stancati:

Andrea Stancati is the Vice President and the Head of GI Global Medical Franchise at Takeda. He has joined Takeda in June 2018 as VP & Global TA Head Gastroenterology Medical Affairs. He served multiple global companies in his career including UCB, Novo Nordisk, Novartis & Roche

Related Post: ViewPoints Interview: QIAGEN’s Kai te Kaat Shares Insights on QIAprep&amp Viral RNA UM Kit

The post ViewPoints Interview: Takeda’s Andrea Stancati Shares Insights on Entyvio (vedolizumab) SC Formulation first appeared on PharmaShots.

ViewPoints Interview: QIAGEN’s Kai te Kaat Shares Insights on QIAprep&amp Viral RNA UM Kit

In a recent interview with PharmaShots, Kai te Kaat, the Vice President, Head of Franchise Oncology, MDx at QIAGEN shares his insights and highlights on QIAprep&amp Viral RNA UM Kit.

Shots:

  • QIAGEN to launch the QIAprep&amp Viral RNA UM Kit, designed to simplify and accelerate PCR swab analysis and remove key testing bottlenecks for Covid-19 and other RNA viruses
  • The kit combines a liquid-based sample preparation step completed in the only 2min. with real-time PCR detection in a streamlined workflow that can be automated with standard lab equipment for any throughput, any assay and any reaction need from single to multiplex testing
  • The workflow takes ~1hr. to deliver a result, compared to ~3hrs. for standard extraction-based quantitative PCR processes and can handle~2,600 samples /8hrs. shift per cycler. The kit complements QIAGEN’s COVID-19 testing portfolio and accelerates PCR analysis for research applications

Tuba: Can we have a detailed discussion on QIAprep&amp Viral RNA UM Kit?

Or

Would you like to discuss the working of the novel kit and how it is accelerating the PCR analysis for research application?

Kai te Kaat: QIAprep&amp is an innovative ultrafast method that combines liquid-based sample preparation with real-time PCR detection for research purposes and/or epidemiological research debottlenecking the detection of SARS CoV2 and other RNA viruses. The end-to-end liquid-based workflow can be automated with standard lab equipment for any throughput, any assay and any reaction need from single to multiplex testing. It can be implemented on all open platforms, typically liquid handlers, and be used in conjunction with any RT PCR cycler such as Rotor-Gene Q, QIAquant, and others. The kit can also be used with a wide range of transport media from Universal Transport media (UTMTM), Viral Transport Media (VTM), or eSwabTM to Virocult®, physiological salt solution, or phosphate-buffered saline (PBS). Besides, it includes a control concept to increase the value of negative results consisting of a human sample control based on RNAse P and B2M genes to indicate the sufficiency of human material in the sample avoiding false negatives and an inhibition control based on artificial sequences to indicate the absence of inhibition by the sample matrix.

Image Source: QIAGEN

The QIAprep&amp workflow is simple, swift, and straightforward, consisting of only three steps: an aliquot is taken from a primary sample (nasopharyngeal, oropharyngeal, or nasal swab) in transport media (8 uL) and added to a sample preparation buffer (2 uL) that is optimized to prepare the viral RNA template without degradation. This is next combined with the RT-qPCR reaction mix (10 uL), which provides reliable and sensitive results for RNA viruses in transport media. The sample then undergoes a routine real-time PCR in a cycler using any assay for SARS-CoV2 RNA detection. The output is finally interpreted, delivering test results in under one hour from start to finish – including incubation and hands-on time – depending on the cycler used.

As the kit only uses three small pipette tips (10 uL and 50uL) per sample, the kit helps to keep consumption of plastic materials to a minimum, and thereby addresses the current major bottleneck of pipette tips at the market while providing significant cost savings by reducing reagent use and labor utilization. In addition, the QIAprep&amp kit can also be used manually with a multi-pipette in lower resources settings or to cover capacity peaks.

QIAprep&amp is a research-based kit and not a diagnostic test and hence cannot be compared to other typical COVID tests that are in the marketplace right now.

Tuba: As mentioned in a press release, QIAprep&amp complements QIAGEN’s efforts to build the broadest portfolio of COVID-19 solutions. Comment over the statement.

Kai te Kaat: Since the beginning of the coronavirus pandemic, we focus on building the most comprehensive portfolio of solutions for COVID-19 testing that addresses the varying needs for clinical and research applications in the fight against the pandemic. These include the production of viral RNA extraction for use on our QIAcube, QIAsymphony, and EZ1 platforms as well as third-party instruments; building up a range of PCR tests on the QIAstat-Dx and NeuMoDx systems that enable COVID-19 detection while analyzing samples at the same time for other respiratory infections and are developing novel easy-to-use solutions for antibody and antigen testing running on a portable device that provides highly accurate results in less than 15 minutes. We are also providing universal next-generation sequencing (NGS) solutions for research use with any sequencer, in particular gene panels integrated with bioinformatics for analysis of the SARS-CoV-2 virus, and are scaling up production capacity for reagents sold to other companies for use in their own COVID-19 tests. With the launch of QIAprep&amp that includes both sample extraction components and optimized PCR reagents for only one procedure we now complement our COVID-19 testing portfolio further removing key testing bottlenecks for SARS-CoV-2.

Image Source: QIAGEN

Tuba: How confidently you can pitch about its accuracy since it delivers results in under one hour?

Kai te Kaat: It is a research-based kit with which we achieve a detection limit of less than 8 viral copies/reaction and a high concordance to established extraction-based methods.

Tuba: What are your other targets except for COVID-19. Are you specifically working on something?

Kai te Kaat: The product is optimized for the mentioned transport media and detection of enveloped RNA viruses such as SARS-CoV2. We are further qualifying additional transport media for the workflow to increase its universal applicability. Further, we are looking into deploying the same workflow for other respiratory viruses.

Tuba: When can we expect QIAprep& Viral RNA UM Kit’s availability for research applications?

Kai te Kaat: The kit is available worldwide for research applications starting the week of October 19th. Since it is a fully liquid-based workflow, scalability in manufacturing is deep with the potential of more than 20 million reactions per month.

The kit is available worldwide for research applications starting the week of October 19th. Since it is a fully liquid-based workflow, scalability in manufacturing is deep with the potential of more than 20 million reactions per month.

Tuba: What do feel was the biggest roadblock in developing an accurate testing solution for COVID-19?

Kai te Kaat: General roadblocks for the development of accurate testing solutions for COVID-19 are the access to defined standard materials and controls as well as overall supply challenges in the industry, especially on plasticware.

Tuba: What all developments and can you count the name of QIAGEN in providing solutions for the COVID-19 to date?

Kai te Kaat: From the onset of the novel coronavirus outbreak, our teams have been working around the clock to ensure the availability of existing testing solutions and to develop new SARS-CoV-2 tests to address international testing needs. Today, we offer the most comprehensive portfolio of SARS-CoV-2 testing solutions on the market, covering the needs of clinical and research customers, from manual to automated sample processing, low to high throughput, single-plex to multi-plex, and from active infection testing to the detection of previous viral exposure. An overview of our global efforts in the fight against coronavirus can be found here; for background information on our coronavirus testing solutions please download our factsheet.

Tuba: Are you planning to further develop solutions for the COVID-19 testing portfolio?

Kai te Kaat: Based on the technology used in the novel QIAprep&amp kit we are currently developing IVD test kits for SARS-CoV2 RNA.

Tuba: Do you want to highlight anything else about QIAGEN for our subscribers?

Kai te Kaat: Today, we offer the most comprehensive portfolio of SARS-CoV-2 testing solutions on the market addressing the varying testing needs in the fight against the pandemic covering the needs of clinical and research applications, from manual to automated sample processing, low to high throughput, single-plex to multi-plex, and from active infection testing to the detection of previous viral exposure. Testing will continue to be a dominant factor in the fight against the pandemic: even when the vaccines will come to market, the immune status of the population will need to be assessed and monitored. Here, PCR will continue to remain the gold standard for the detection of SARS-CoV-2 and other RNA viruses, and with our QIAprep&amp technology, we made it even faster without compromising performance.

 About Kai te Kaat:

Kai te Kaat is the Vice President and the Head of QIAGEN’s Oncology Franchise in the Molecular Diagnostics Business Area.  He has joined QIAGEN in 2005 as the Global Business Director Proteins. He has been working for the last 11 years at QIAGEN

Related Post: ViewPoints Interview: Eli Lilly’s Dr. Lotus Mallbris Shares Insights on Baricitinib

The post ViewPoints Interview: QIAGEN’s Kai te Kaat Shares Insights on QIAprep&amp Viral RNA UM Kit first appeared on PharmaShots.

ViewPoints Article: Digital Healthcare in India – Current Trends & Future

Digital healthcare means using communications and information technologies in medicine to diagnose, predict, treat, and monitor diseases. It is also widely used for prognosis, rehabilitation, behavioral health, and public health.  Indians have witnessed a surge of smartphone and internet use since the last decade. This had led to an easier delivery of smart digital solutions. Known inequalities in access to healthcare, lack of trained professionals, outdated infrastructure, and low healthcare budget are some of the problems in India. Modern healthcare technology and innovation is the solution to improve the health status of the country. Similarly, the healthcare system is continuously being transformed with the latest technology. It is believed that in the coming decade, all pharmaceutical companies will leverage available technology to improve clinical outcomes.  India`s healthcare industry has grown from $100 Billion (2015) to $280 Billion (2020) and is rapidly surging at a CAGR of 18.3%

Amidst Covid-19, there is a fortunate surge in innovation and locally made technology in India. The government is enthusiastic about digital solutions for rapid diagnostic methods among other innovations. Technology should be consumer-friendly, efficacious, and affordable. India is not far behind in terms of innovation.

The objectives of digital health products and services are: 

  • To improve clinical outcomes
  • To improve the patient experience
  • To be consumer-friendly
  • To improve the physician provider experience.
  • To address health problems 

Need of Digital Technology to Manage Health

A plethora of issues exist in India`s healthcare sector which are still untouched by digital technology. Antibiotic resistance, medical reimbursement, TB, malaria, diabetes should be targeted in the coming decade.

The ratio of patients to doctors is below the acceptance rate. India does not meet minimum WHO recommendations for the healthcare workforce and infrastructure.

Image Source: PwC Analysis

In short, Digital healthcare is needed for the following:

  • To improve access to healthcare
  • To reduce healthcare inefficiency
  • To improve the quality of care
  • To lower the cost of healthcare
  • To Provide individualized health care

Current Scenario

India is climbing the peak of the digital health revolution. The majority of healthcare professionals (HCPs) use electronic medical records (EMRs) for more efficient medical practice.

For a few years, novel digital solutions are gaining popularity with joints from private and public sectors. The government has recently launched the much needed National Digital Health Mission (NDHM). The private sector has rolled out mobile apps, telemedicine, research centers among other initiatives. Telemedicine, Artificial Intelligence (AI), mobile apps, robotics, and virtual reality (VR) are gaining popularity. Digital intervention in healthcare is expected to drive the industry at a CAGR of 23% by 2020.

India is climbing the peak of the digital health revolution. The majority of healthcare professionals (HCPs) use electronic medical records (EMRs) for more efficient medical practice.

Top 10 Digital Health Solutions

  1. M-health: A simple mobile app that provides online video consultation and an added feature to book laboratory tests online. It has an estimated market size of 5,184 crore INR in 2020.
  2. Remote diagnosis – These products provide point-of-care diagnostics, teleconsultation, and online prescription capabilities thus increasing access to healthcare in rural areas. For example, a wireless monitor that measures blood pressure, oxygen saturation, pulse, body temperature, blood sugar, blood cholesterol, and total hemoglobin (Hb) count with a mobile application on your smartphone. It is expected to grow at a CAGR of 20%.
  3. Telemedicine – It is the use of digital technology for remote diagnosis, monitoring, and patient counseling. The high volume of patient load (millions) on a few doctors (thousands) may burden the whole system and reduce its efficiency. Telemedicine or Virtual consultation will enhance patient experience and engagement; fewer tests would be prescribed; the rate of hospital re-admission will be less; better medication and patient adherence would lead to desired clinical outcomes.  It is a rapidly emerging sector in India and the telemedicine market in India is expected to reach $32 million by 2020
  4. Digital Connectivity – support groups and knowledge portals for patients and digital chatting platforms for medical professionals.
  5. Wearables – They are used to measure basic health parameters such as heart rate, number of steps, sleep pattern, etc. For example, exercise trackers, oximeters. The overall market for this is currently valued at 30 crore INR.
  6. Big Data Analytics – Healthcare players have realized the value of combining consumer insights and internal company data to optimize their products. Advantages are a) lower rate of medication errors, b) Facilitating Preventive Care c) More Accurate.
  7. Artificial Intelligence (AI) – It helps in automation of clinical tasks and virtual nursing assistants. AI has the capability to transform health management. It is used in precision medicine, medical imaging, drug discovery, and genomics. DeepGenix helps the user in understanding their problems based on questions and then predicts the diagnosis. It uses deep phenotyping and deep learning (a form of AI).
  8. Electronic medical records (EMR): This should help reduce medical errors and improve health outcomes. Automated patient history has a lot of benefits. Arintra, an AI-based software incorporates branching techniques to collect and store patient history. It also helps in diagnosing and suggesting laboratory tests. It can also be used in telemedicine before the consultation.
  9. Virtual reality – Surgeons are using virtual-reality simulations to improve their skills or to plan complicated surgeries. 
  10. Blockchain – It is proven to be effective in preventing data breaches, improving the accuracy of medical records, and reducing costs.
Image Source: PwC Analysis

Future

Digital healthcare will continue to remain an essential part of healthcare in India. Now medical tasks like analyzing radiology, pathology, or ophthalmology images are performed by computers. Telemedicine, E-pharmacy, fitness apps, wearable devices have become an integral part of the patient`s lives, especially during Covid-19.

Opportunities for the future

  • Electronic medical records (EMRs)
  • Robotics
  • Smart health monitor
  • Mobile health apps
  • Computer processing
  • Genomics
  • Virtual Reality (VR)

Though some innovations are still in the early stages, they look promising. For example, research on 3D-printed hearts and other organs is being carried out; doctors are using VR instead of medication to treat pain; robots are being used in surgeries; genomic analysis. The need for digital innovations has become even more urgent during the Covid-19 pandemic. 

Conclusion

There is a significant need for digital technology to bridge healthcare gaps. India holds the potential for digital growth, given its innovation rate, identification of problems, growing population, and surging healthcare industry. Digital technology will help India achieve healthcare for all and will soon emerge as a global leader in digital health.

References

  1. PwC Digital Health Whitepaper: Indian Healthcare on the cusp of a digital transformation.
  2. Digital Healthcare in India
  3. Digital Health

Related Article: ViewPoints Article: Digital Revolution in Healthcare and Strategic Role of Medical Affairs Amidst Covid-19 Outbreak

The post ViewPoints Article: Digital Healthcare in India – Current Trends & Future first appeared on PharmaShots.

ViewPoints: Medical Representative Opinion Survey for Business Continuity with New Normal

K. K. Consulting Services has conducted this survey by contacting around 2200 medical representatives accros the india uisng google forms.

Objective of 

The purpose of this survey is to design a platform for pharmaceutical sales professionals (PSP) to share their opinion about business continuity challenges faced by them due to the present COVID pandemic situation. The nature of the job for Pharmaceutical sales professionals is primarily field sales, which is meeting doctors and promoting medicines of companies and generating new business. Due to corona risk, field sales have become more challenging, and going out of the house may not be safe. Moreover, doctors are not finding it safe to meet pharmaceutical sales professionals to avoid the risk of corona infections to patients as well as hospital/clinic staff and from staff/patients to PSP’s.

With these challenges, there is pressure from company/reporting managers to work in the field and meet doctors for generating more business. Some companies are taking adequate measures for PSP’s to protect them from infection.

Understanding these circumstances, what is the opinion of Pharmaceutical Sales Professionals? How are they ensuring business process continuity? Are they willing to work in the field by taking risk of their health? For questions like these and more, this survey aims to seek opinion with the response to MCQ’s. The aim is also to give support to the voice of Pharmaceutical Sales Professionals by bringing it to the notice of key stakeholders of the Pharmaceutical Industry

Methodology

This survey was conducted by the circulating link of Google Forms using social media. Participants had to choose the response from the given options and submit the form. It was a set of 11 questions with respect to survey title and demographic details. We compiled the information generated from participants and published it. No personal information is collected from any participant.

Outcome of the survey

Around 50% of survey participants have more than 10 years of professional experience and around 59% of total participants are working as team managers. This shows that the opinion shared by participants who have a good understanding of the business process and customer connects. (n=2206)

  • Sending messages over “WhatsApp” was a preferred way of keeping in touch with doctors, Call doctors and promoting products was the 2nd preference. Surprisingly around 22% of PSPs choose not to keep any engagements at all with doctors.

  • 75% of participants feel that it will take around 0-6 months’ time to start sales call like it was happening before COVID 19 pandemic.

  • Successful engagement with doctors with the help of online tools is a long-standing task for the pharmaceutical industry, due to the corona pandemic, companies are not left with any other option other than trying this. Perhaps all these initiatives are implemented in a hurry and therefore poor response is observed.

  • To maintain engagement with doctors, many companies conducted webinar/Facebook live events for sharing knowledge. In the survey, it is found that the effectiveness of such meetings was poor. 70% of participants feel that it’s not effective.

  • The productivity of such meetings is also not seen; 78% of participants feel that online webinar/FB engagements do not have positive impact on business growth.

  • 60% PSP’s suggested that they are pressurized by reporting manager/company to go in the field and meet doctors. This pressure is observed most at 63% in the east zone and least at 57% in the west zone. Team managers across India felt more pressure then Medical Representatives.

  • Fear of losing a job due to COVID 19 pandemic was also observed, 72% of PSP’s voted for it. Team managers have more fear then Medical Representatives. If this of losing a job is divided among 4 zones, then it’s observed less in the south at 69% and most at North and East zones at 74%

Zones

1 West – Maharashtra, Goa, Gujarat, Madhya Pradesh, Chhattisgarh

2 North – Rajasthan, Haryana, Punjab, Delhi NCR, J & K, Himachal, Uttar Pradesh & Uttarakhand

3 East – Jharkhand, Bihar, West Bengal, Orissa and North East states

4 South – Andhra Pradesh, Telangana, Tamilnadu, Karnataka

Disclaimer

The opinions expressed in the survey do not reflect the opinions of KK Consulting Services or its Editors/Publishers/Sponsors.

Information contained in published results has been obtained from the survey. However, no author’s guarantees the accuracy or completeness of any information published herein and no authors shall be responsible for any errors, omissions, or claims for damages, arising out of use, inability to use, or with regard to the accuracy or sufficiency of the information contained in the publication.

No responsibility is assumed by the Publisher or Editors for any damage to persons or property as a matter of negligence, or otherwise, or from any use of information by any methods, product, instructions, or ideas contained in the published material. Information in this publication is as of date 6th July 2020.

All rights reserved. No part of any published work may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher/author.

Image Source: Ind-Swift Lab

ViewPoints: COVID-19 Vaccine Distribution the Next Supply Chain Frontier

An overview of various aspects of the supply chain that would be crucial in the production and distribution of COVID-19 Vaccine. Write to us at [email protected] if you want a PDF copy of this report.

Over the past seven months, the global pandemic caused by the spread of SARS-CoV-2, the virus that leads to coronavirus disease (COVID-19), has impacted the global economy and people’s lives tremendously. A number of countries and companies have concentrated their resources to produce a vaccine for COVID-19 and considering the present scenario, one can be hopeful to have a vaccine available soon. However, finding the vaccine is just the first step. Other critical steps that every government should be thinking about in relation to their national vaccine strategy are product integrity and safety, public education, and the actual distribution program itself.

Product integrity and safety tests that assure the vaccine is safe to use, communication programs that inspire public confidence, and a robust supply chain management strategy that anticipates local demand efficiently which will deliver a vaccination program that the general population is willing to participate in. Since the sense of urgency is critical, governments all over the world should start planning based on these important enablers. Without this planning, the goal of having a confident and vaccinated population ready to return to “normality” and participating fully in the economy will not become a reality.

On Tuesday 11th of August, Vladimir Putin announced the first vaccine to the world, named Sputnik V. With this announcement the race to get a working vaccine to people all over the world has heated up further between key players all over the world eager to cash in on this opportunity for financial and political reasons. One thing is clear, whichever vaccine makes it to commercialization the supply chain will play an integral part in the upstream manufacturing supply chain and the downstream distribution.

Some of the key contenders for the Covid-19 vaccine are:

 

Demand for the Vaccine

Many experts around the world are expecting the introduction of these vaccines to cause major challenges to global supply chains in manufacturing, transportation, and distribution as companies scramble to meet demand from countries all over the world. The demand for this vaccine will be at a historic high. Never in the world before has there been a situation where a vaccine needs to go out to the whole world at the same time. With a global population of more than 8 billion people, this will be more than a mammoth undertaking.

Image source: Canva

Upstream Manufacturing Supply Chain

To get to making a vaccine, there are several manufacturing steps that need to be taken which although invisible to most people are critical in the time path to a final drug product. These include making and testing the API product which forms the active ingredient of the drug. Making the actual drug itself (drug substance), the filling process involved in turning the bulk drug substance into usable vials or syringes for vaccination. The other needed parts related to the syringe itself, the needle, the vial, the cap, the label, etc. The last step is the actual final labeling and packaging of the vials into the finished product. In the pharmaceutical industry, all these manufacturing steps are usually performed at different factories often across different countries in the world. Synchronizing these production steps and the availability of all the components, the ingredients, and manufacturing capacity, as well as the logistics between the various factories all, create potential bottlenecks and risks.

Procurement of Vaccines – Access Rights  

Image source: Business Standard

Governments around the world are competing to get first access to available vaccines. They are faced with critical questions around which vaccine brand to back now to secure access to large quantities to be able to start domestic immunization programs. Backing a vaccine and paying upfront for access and guaranteeing certain quantities of doses whilst there is no advance guarantee the vaccine will work is a large financial and political risk only the richer countries are able to make. The US, clusters of countries in Europe, and some other richer nations are making these types of advanced access agreements with key manufacturers. These funds help finance the manufacturing work already started whilst the vaccines are still being developed and tested for approval.

Although it is good that some of the richer nations have stepped up to help pre-finance these vaccine programs it presents a real moral dilemma once the vaccines are approved in terms of which countries get first access rights and which ones do not. Given the share volume of vaccines that need to be produced to cover the whole global population the difference between being a “first mover” country versus a “last mover” could be as long as 3-5 years.

In other words, countries with more money will buy priority access to vaccine programs whilst emerging countries will not be able to do so financially. It will mean that as the world moves out of the COVID-19 lockdown phase, clusters of countries can do so more easily than others. It will create a further disparity between regions around the world economically which potentially poses new socio-economic and (geo) political risks.

Downstream Supply Chain

Image source: CNBC

Once a vaccine has been produced it is ready to be shipped under heavily regulated and temperature-controlled conditions to countries around the world. Many industry experts predict this enormous logistics task will lead to huge capacity problems for airlines and logistics companies. Laurent Foetisch, Supply Chain Management Consultant as Supply Chain Operations with more than 35 years of pharmaceutical manufacturing and logistics experience argues differently. “It is not possible to produce the quantities of vaccines needed all at once. Typically, vaccines are produced in batches of around 100,000 – 150’000 vials/syringes based on a daily production cycle. Even if multiple filling lines are used across various manufacturing locations it is not possible to produce all the vaccines immediately at these numbers in millions for everyone”.

This also means that the “big bang” launch theory of a vaccine might not be as big as many predict. It would mean that availability of vaccines for distribution is spread over a longer time frame which from a capacity perspective is less complicated to manage by logistics companies and airlines. Rather than a “bulk” shipment program, it could well turn more into a “Just in Time” shipment program feeding into domestic immunization programs.

However, there are other factors to think about as the first batches of vaccines are released and shipped. Eelco Dijkstra, Managing Partner at Europhia Consulting points out that ensuring product security across the entire supply chain will be vital. Not just in terms of establishing and using validated temperature-controlled transport and storage solutions but also in terms of risks such as the product being “highjacked” and/or “counterfeited” by organized crime as the product is transported across multiple countries.

National Vaccination Program – The Final Mile Distribution

Image source: Medical Express

 The two major challenges of the government-run vaccination program on a national level would be in public education and in the distribution program itself. To make any vaccination program successful, it is vital to plan on how to educate the end community to ensure that the public is fully aware prepared to take the vaccination timely and efficiently.

Talking about the distribution strategy, the key questions that need to be addressed include how to best manage any vaccination program. The biggest first question for governments to address is whether a vaccine will be made mandatory for the whole population or be voluntary? Who will receive vaccination first? Vulnerable groups first such as people with a medical condition or the elderly? Will governments use hospitals throughout the country for people to come to and get vaccinated or will government look to use more points of vaccination such as medical clinics including private ones?

In some countries it will make sense to use existing COVID-19 infrastructure such as dedicated clinics and testing centers already in place. In some cases, it might make sense to set up “mobile” vaccine units which come to elderly homes, local community centres and schools.

Vaccines are pharmaceutical drugs and will need tight temperature and security control during storage and transportation. Given the share size of any vaccination program based on population size, it will run into the millions of vaccinations for which an end to end distribution model will need to be designed, tested, and executed in a very short period of time. Therefore, the timing for the planning for such a distribution model cannot start soon enough. For any vaccination program to be successful, the distribution part will be critical. Therefore, any national distribution plan linked to a country’s vaccination program will need to involve partnerships between government and private companies in logistics and distribution to plan and execute. We are already working with several governments on these initiatives providing input on strategic and tactical elements of such distribution plans.

Disclaimer: The opinions are based on the author’s own experience and understanding of the dynamics within the sector.

Europhia Consulting is an international management consulting company specialized in the logistics and supply chain industry in the life sciences sector. We operate global assignments for our clients.

Supply Chain Operations SA, based in Switzerland, is a specialized healthcare supply chain consultancy firm created in 2011 to serve the biopharmaceutical and Medtech industry.

We bring more than 120 years of end-to-end supply chain expertise to our valued customers. Both companies work together on strategic assignments for clients globally. We do not pretend to have been able to capture all challenges and all insights and have deliberately focused this strategy paper on some of the key challenges we see based on our work with clients within the industry.

For any questions or comments about this strategy paper please do not hesitate to reach out to us.

Eelco Dijkstra

Eelco Dijkstra of Europhia Consulting has worked in supply chain and consultancy for over 25 years and in recent years has focused his expertise on the global pharmaceutical sector. He as worked a number of years for TNT Express and Kuehne & Nagel and in recent years managed his own consultancy practice. 
Mobile: +31 624661688 
Email: [email protected] 
Website: www.europhia.com  

Laurent Foetisch

Laurent Foetisch of Supply Chain Operations has extensive experience as a supply chain executive responsible for managing a global biopharmaceutical company in Switzerland for more than 20 years. In 2007 Laurent managed the supply chain integration between Merck and Serono with the responsibility to create one central supply chain structure using common processes and tools. Since 2011, Laurent runs its own supply chain boutique consulting firm named Supply Chain Operations SA. 
Mobile: +41 792052332 
Email: [email protected] 
Website: www.supplychainoperations.ch

PharmaShots ViewPoints: Revised approach for First Aid during and after the Catastrophic Pandemic – Safe and Saving

The SARS CoV-2 or COVID-19 pandemic has changed human life permanently. Hence, a few critical areas need revisiting in light of these changes to set a “new normal” for them. One of such areas is first aid. Correctly given first aid helps victim of an emergency episode of a disease or an accident prevents damage and thereby disabilities and often saves life.  While the post-pandemic world changes the social behavior, diseases and emergencies continue to influence the human life in the same way. In fact, with less visits to hospital and significant healthcare resource consumed by the pandemic, need for first aid is enhanced. However, the nature of infection of SARS CoV-2 requires revisit the first aid practice to ensure safety of both, the rescuer and the victim.

There are multiple advisories and instructions issued by authorities on this matter, including National Safety Council of America, American Red Cross, St. John Ambulance, St. Andrew First aid, European Resuscitation Council, etc. On the other side, there is a debate about whether CPR is safe during the SARS CoV-2 global outbreak, also known as COVID 19 Pandemic. However, most of these literature focuses on Cardiopulmonary resuscitation (CPR) and a few on psychological first aid, which may not be enough in the current situation of a highly spreading contagion.

Hence, this article discusses about top 10 changes in the first aid practice in the local context.

1  Be more prepared

1.1  Keep yourself informed and updated

SARS CoV2 infection and multiple unidentified risks, which the authorities are publishing time to time. A first aider must remain updated about risks, treatment, first aid approach, advisory and instructions by referring to websites and news feed. In addition to the national emergency helpline numbers, there may be some helplines for COVID-19. One important aspect that may go unnoticed is changes of emergency contacts.

1.2 Carry and use Personal Protection Equipment (PPE) where possible

A First aider is at a high risk of exposure to coronavirus infection. Hence, it is important to use PPE. However, if PPE is not available, it is advised to use full sleeves apron or an additional over cloth (like a shirt or jacket over already worn clothes).

1.3  Carry extra gloves, extra mask, fluid resistance Mask/towel

A first aider willing to serve during the pandemic situation should try to carry multiple PPE. At least, should carry multiple gloves and masks, especially the fluid resistant masks or clothes. 

1.4 Use disinfectant spray, a spray of disinfectant mouthwash

Disinfection is the key of prevention of coronavirus infection. Hence, even for personal hygiene use of sanitation production is strongly recommended. Hence, along with hand sanitizers it is important for first aiders to carry and use spray sanitizers and the mouth sanitizers.

2   Changes in First aid infrastructure and equipment availability

2.1  Changes in the composition of the first aid box in vehicles etc.

A new first aid box must include some additional material beyond the routine equipment and materials. These new additions are – PPE Kit, Masks (minimum 2), Gloves (minimum 4 pairs), face shields, disinfectant spray, mouth disinfectant, sealable bag, fluid resistant clothes and plastic sheets, women-sanitary pad or absorbent diapers and bag valve mask breather.  In addition, it is advised to keep touchless thermometer and SPO2 sensor in the First Aid box.

2.2  Oxygen cylinders to be made available at all establishments like ATM, Bank, community places

Like the fire extinguishers are placed in all notified places such as banks, vehicles running on gas, ATM rooms, community centers, offices, there must be a provision of placing oxygen cylinders with disposable masks.

2.3 AED or mechanical CPR equipment to be available in public places

For Cardiac Arrest AED is an important therapy. However, there is some level of risk attached to it.

3 Reframe risk assessment

The lay rescuer / trained non-medical first aiders are usually the first level persons to reach the casualty. Hence, the first aider must suspect every case as a SARS (Corona infections of all types) case unless confirmed otherwise. First change is to start with assessment of  level of COVID Risk of the area.  Applications like goggle maps are useful often. Some countries practice placing signage to indicate risk zones. In addition, the pandemic calls for a multilevel additional assessment to check for COVID-19.  Especially, the first aider must assess the risks of cross contamination, like if there are some body discharges around or on clothes of the casualty including spits, sputum, saliva, blood, vomitus etc.

In addition to risks also need to check for resources like first aid box, resuscitation machines, oxygen cylinder etc. Their appropriate use will help maintain safety.

4 Unlearn and Relearn First Aid skills

First aiders are traditionally trained to assess surrounding, casualty etc. However, SARS COV2 is a contact-spread infection. Hence, the first-aiders need to avoid a few important first aid techniques consciously, that deemed best suite before set up of the pandemic.

4.1  Staying Safe while giving first aid during the pandemic

While we discussed multiple changes so far, there are several personal responses, which are important to remember and execute at all times. Few of them are a repetition of what is stated already

  1. Tell the crowd to maintain social distancing or to completely disperse.
    1. Use enough protection. If there is PPE kit, use, if not, use apron, overcoat or plastic sheet to cover the first aider
    2. Minimize provider exposure, Do not touch a wound or any of the body fluids, exposed dressings, pads, etc. Also, do not touch anything that is meant to touch patient’s sensitive areas esp. face, wounds, etc.
    3. Sanitize hands and face of rescuer and first aider before checking for eyes, tongue, and breathing 
    4. Disinfect immediately before and after the procedure

4.2   Changes in the casualty assessment and response

  1. Do not touch any part and surroundings of a casualty with bare hands.
    1. Do not check to breathe by placing an ear near the nose to avoid close proximity. Instead, use trusted mobile apps to monitor vitals like SPO2, Blood pressure, Heart rate, and respiratory rate, except when cardiac arrest is suspected.  
    1. Use of Shepherd (Figure 3), Sylvester (Figure 1), Holgar-Nelson methods (Figure 2) where possible than using mouth to mouth or mouth to nose ventilation except for cardiac arrest.
    1. In case of conditions like epileptic seizures, cover the patient’s body first before holding the limbs or provide disposable soft support to avoid injury. In both these conditions, avoiding exposure to anybody’s fluids is extremely important. 
Source: https://lorenamontes1234.wordpress.com/2013/07/02/health-product-review-other-methods-of-artificial-respiration/

4.3   Differences in methods of carrying

Usually, when a first aider carries a casualty, in any position (fireman’s lift or back-mount) carrier’s face is exposed to risk. Hence, it is important to over the casualty correctly with a fluid resistant clothes or plastic sheets etc. and use face shield to minimize exposure. In two or more persons carry (stretcher, fore and aft etc.) the risk to carrier is relatively less. However, in this case, for security of the casualty from exposure to external droplets, it is important to cover the casualty properly.

5 Safe Disposal of all exposed material

Safe disposal of all exposed material is now a part of first aid. While earlier it was fair to dispose the bio-waste into safe trash, now the definition has included many critical aspects All exposed material and not just bio-waste, including PPE, Masks, kit materials like cotton, dressing, overclothing must be removed immediately after first aid, disinfected, and store in a sealed disposable bag before handing them over to biohazard disposal team. No material to be left unattended even after disinfection. The clothing must be laundered immediately if possible. The area of the casualty must be correctly disinfected after removal of the casualty.

6 Safe Cardiopulmonary Resuscitation  (CPR)

Source: https://www.jaypeedigital.com/book/9788184484403/chapter/ch6

6.1  Hands-only CPR continuous compressions at a rate of at least 100–120 min

Hands only CPR is chest compression at rate of 100 – 120 chest compressions per minute with inspection of airway and as needed extension of neck every minute. The C-A-B steps should be followed as otherwise, but Mouth to mouth ventilation to be avoided unless extremely necessary. Sylvester method may be used  in stead of mouth-to mouth / nose ventilation.

Fig 1: https://www.slideshare.net/rajendra9a/artificial-respiration-66248377

6.2   Use water absorbent, fluid-resistant mask

If mouth-to-mouth respiration is inevitable, water absorbent, fluid resistant mask or cloth in multiple folds for both rescuer as well as for the casualty must be used. The mouth and face of both the rescuer and the casualty must be sanitized with spray disinfectant.

7. Safe Road management of accidents, injury, wound, and blood handling

7.1  Care of wounds and bleeding

First aid for bleeding continues in the same hierarchy with elevation with direct pressure, pressure points and tunicates as first, second and third line of treatment. However, it is important to continue keeping complete aseptic precautions while handling the wound. No wound should be touched with open hands. There should not be any pre-exposed dressing for the wounds including open fractures. All rescuers must wear mast and gloves at all times and all other persons must stand at least 2 meters away from the casualty. The safe disposal and post-removal sanitation must be practiced. 

7.2   Care for Close fractures

There is no difference in handling the close fractures. However, the sanitation and safe disposal with social distancing must be practiced.

7.3  Other bleeding

For visible / diagnosed internal bleeding ice-cold water bath or ice-pack must be applied in as is conditions. In case of vomiting of blood the patient should be given ice-cold water to drink. In vaginal bleeding, the patient should be given comfortable sitting position with pad. However, the most important aspect is anything that is provided to the patient, must be sanitized at all levels and all the immediate handlers must sanitize their hands well. All the discharges must be well disinfected as soon as possible.

8  Safe first aid for respiratory conditions

Fig 3: https://www.flickr.com/photos/[email protected]/20402935893

8.1        Infectious and acute respiratory conditions

In case of acute respiratory conditions, risk if SARS COV-2 is the highest. Hence, the patient must be asked to wear double mask, face shield and disinfect his clothes, hands and face. The rescuer must wear PPE before handling the patient. If there is breathlessness, patient must be made to sit on a chair with head rested on back with extension. If oxygen cylinder is available, patient must be given oxygen to breath. COVID 19 helpline must be immediately called for further help. The rescuer must follow the diagnosis of the patient. If the patient is tested positive or is a suspect of coronavirus infection, the rescuer must go for isolation and testing.

8.2   Acute Exacerbation of Asthma

In case of acute exacerbation of asthma, the patient should be given moral support, with some instructions from the social distance, unless the patient looks to have an emergency need. In emergency need, the patient should be given bronchodilator and comfortable position with moral support. All the procedure must be with minimum PPE (Gloves, mast and face shield) and after handling the patient and his belonging, hands must be sanitized with change of gloves.

9   Safe First Aid in shock, stroke, heart attack

First aid approach for critical conditions like shock, stroke and Heart attack is changed to include disinfection and PPE use and social distancing before start of the first aid. While all these three are emergency situation, all three are extremely susceptible to infection of SARS CoV-2 Infection. Hence, the patient requires more than usual care to avoid cross contamination. Hence, the first most important step (may be even before first aider prepares with PPE, the crowd must be pushed back more than 3 meters and with the help of a reliable assistant (family member, PPE / safety gear wearing security guard or a person from forces etc.) the area around must be disinfected).

Another critically important point in all these three conditions is that the patient must not be given mask to wear (in fact, this makes the patient more vulnerable to infection). Use of a transparent face-shield is highly recommended. If the patient is conscious or in stupor, patients hands and face must be immediately sanitized. Critical points of changes in the first aid include:

9.1   Changes in shock first aid approach

  1. While giving heal-low position to the patient, place a clean paper / plastic sheet under to avoid contamination from down.
  2. While loosening the clothes, start immediately after sanitizing hands. Follow sequence Face, Head, chest, waist, feet.
  3. While providing a patient a warm cover, use a fresh disposable sheet below the cover and disinfect the warm cover with a spray disinfectant
  4. Rest head tilted on side on an absorbent pad (sanitary pad in women hygiene or absorbent diaper is the best)

9.2   Changes in the approach for stroke first aid

  1. If there is any active bleeding, vomiting, plasma or nasal discharge, wipe it only with the absorbent pad or a fresh absorbent cotton.
  2. If CPR is needed, use low pressure oxygen or bag valve mask breather instead of other artificial method. If heart function is normal and the patient can be laid down, use chest compressions for breathing. Avoid moving limbs, especially if they are week.
  3. Do not give anything including blood pressure lowering drugs orally. Rather reach the nearest medical center.

9.3  Changes in approach for heart attack first aid

  1. The first aid for heart attack remains grossly the same, with a few precautions to avoid cross infection.
  2. There is a high possibility that the low oxygen saturation mimics symptoms of heart attack. Hence, it is important to have all safety precautions

10    Psychological first aid

Psychological first aid is an emerging technique, which has immense importance in the current pandemic situation. There is an increasing number of psychological casualties due to fear, anxiety, or depression due to many reasons including loss of wedges, increasing incidence of stress-related complex, etc.  There is a good informative article by  George S. Everly, Jr. on this topic. That must be read and comprehended.  A solution like digital pet could be a good option.


Refrences

[i] First Aid Technical Bulletins

[ii] Coronavirus (COVID-19): Prevention & Safety Information for Students

[iii] Covid-19: advice for first aiders

[iv] How to Perform CPR During the Coronavirus crisis

[v] European Resuscitation Council COVID-19 Guidelines

[vi] Psychological First Aid

[vii] Exploring new frontiers in mental health care with digital technologies 

Dr. Ashish Indani

Dr. Ashish Indani is a physician and currently working for Tata Consultancy Services as a domain consultant for Life Sciences Platforms. He holds a long experience in conducting first aid training.

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