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.

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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.

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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.

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