Biohaven’s Troriluzole Failure; Daiichi/ AZ’s Enhertu; Fujifilm & Manufacturing Spree; J&J’s Darzalex Faspro

Biohaven’s Troriluzole Dwindles Again In Alzheimer’s After Anxiety 

Biohaven Pharmaceuticals had put too much faith in its third-generation prodrug, Troriluzole. The company has tested the efficacy of the drug in more than one indication, including generalized anxiety disorder (GAD), obsessive-compulsive disorder, spinocerebellar ataxia and Alzheimer’s disease (AD). However, it seems the drug continues to disappoint the company one after another.

After the drug failed to produce better outcomes in anxiety, failed to meet primary outcomes in OCD, the company announced that their chemical entity that modulates glutamate, the most abundant excitatory neurotransmitter in the human body, has even flunked in Phase 2/3 clinical trial as a symptomatic treatment in mild-to-moderate Alzheimer’s disease (AD). 

Thus, the company has decided to wrap up the trials for AD. This is not something new in the Alzheimer’s disease market. Despite the availability of scientific evidence, extensive R&D, and investment of huge amounts, no new drug has managed to walk the carpets. Several have failed and abandoned with the plight and the cost of the disease seemingly growing with each year passing. 

A Sweet Year For Daiichi/ AZ As Enhertu Gets FDA Approval For Gastric Cancer

The U.S. Food and Drug Administration has given the nod to Daiichi Sankyo’s and AstraZeneca’s Enhertu (fam-trastuzumab deruxtecan-nxki) for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen.

Enhertu is an antibody-drug conjugate (ADC) that comprises a humanized anti-HER2 IgG1 monoclonal antibody. The approval is based on the positive results from the randomised Phase 2 trial conducted in Japan and South Korea. 

With the approval, Enhertu has become the first HER2-directed medicine approved in a decade for patients with HER2-positive metastatic gastric cancer. It is already approved for adults with unresectable or metastatic HER2-positive breast cancer who have had two or more previous anti-HER2-based treatments in the metastatic setting.  The company has future plans to pursue the trials for the drug across a broad range of HER2 targetable cancers.

Fujifilm Increases Legroom In Cell And Gene Therapy, Plans For New Manufacturing Facility  

Fujifilm and the Center for Advanced Biological Innovation and Manufacturing (CABIM) has secured USD 76 million in financing and also signed a lease for a 40,000 square-foot site in Watertown, Massachusetts at The Arsenal on the Charles, owned and operated by Alexandria Real Estate Equities. 

CABIM, the industry-academia research and development consortium, is a joint effort of Fujifilm, Harvard University, Massachusetts Institute of Technology, Cytiva (formerly part of GE Healthcare Life Sciences), and Alexandria Real Estate Equities, Inc. CABIM plans to help make new therapeutics, medicines, and technologies accessible to patients and strengthen Greater Boston’s position as the world’s life science capital. The plan is to build eight clean rooms, with a configuration to produce both cell and viral vector products within the physical space. 

Fujifilm is trying everything to build its position in the cell and gene therapy domain even stronger. With its CDMO arm, Fujifilm Diosynth Biotechnologies exploring more in-depth into the domain, and showing a shited interest in its viral vector capabilities for Covid-19 vaccines, will procure GMP2 contract process development and manufacturing services as part of its role in the new manufacturing and innovation centre.

J&J’s Darzalex Faspro Receives FDA’s Blessings For Amyloidosis

Janssen has announced that its Darzalex Faspro has received the USFDA approval for adults with newly diagnosed light chain amyloidosis. The drug was originally developed by Genmab in 2012 and was in-licensed to Janssen. 

Darzalex Faspro is a combination of daratumumab and hyaluronidase-fihj, a subcutaneous formulation of daratumumab. It is the only CD38-directed antibody that has got approval for subcutaneous injection for multiple myeloma, and now it has been given the nod for AL amyloidosis. The drug is approved in combination with bortezomib, cyclophosphamide and dexamethasone (D-VCd) and is the first and only FDA-approved therapy for patients with this indication. 

AL amyloidosis affects over 4000 people each year in the US, and about 30% of patients with AL amyloidosis die in the first year after diagnosis. Today’s approval is nothing less than a breakthrough in the AL amyloidosis market. 

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Birinapant licensing; AvantGen, IGM pairs up for anti-SARS-CoV-2 antibodies; BeiGene, Novartis to co-dvelop Tislelizumab; Valo raises USD190 M; Bluebird Bio Spins-off

Medivir, IGM Biosciences enters into an exclusive licensing agreement for Birinapant

Medivir AB has entered into an exclusive licensing agreement with IGM Biosciences to receive global, exclusive development rights for Birinapant. Birinapant is a clinical-stage SMAC mimetic that degrades Inhibitors of Apoptosis Proteins (IAPs) by binding to them, ultimately leading to cell death in tumor cells. 

Further, Birinapant also complements the anti-tumor activity of the immune system. Thus, the drug appears to be a promising therapeutic agent in treating different forms of cancer in combination with other drugs. IGM-8444 is another drug that is currently being tested in a phase I dose-escalation study in patients with solid and hematologic malignancies by IGM Biosciences. It is an IgM antibody targeting Death Receptor 5 (DR5), and IGM is hoping to test Birinapant with IGM-8444 for the treatment of solid cancers later this year. 

As per the terms and conditions of the agreement, Medivir is eligible to receive an upfront payment of USD 1 million, followed by an additional USD 1.5 million after Birinapant successfully becomes a part of the Phase I trials. Medivir is also eligible to receive milestone payments up to a total of approximately USD 350 million, plus tiered royalties up to mid-teens on net sales upon the commercial approval of the drug. 

AvantGen Enters into a Licensing Agreement for its Anti-SARS-CoV-2 Antibodies with IGM Biosciences 

AvantGen has announced the licensing of a panel of its anti-SARS-CoV-2 antibody clones to IGM Biosciences for COVID-19 therapy development. It is a panel of high-affinity human monoclonal antibody clones, which binds to two distinct epitopes on the receptor-binding domain of the SARS-CoV-2 spike protein, thereby blocking the spike protein from interacting with ACE2. This eventually averts virus-induced cell-killing, also known as cytopathic effect.

Under the licensing agreement, IGM Biosciences receives the rights to convert the antibody clones into IgA or IgM format for further development for the treatment of COVID-19. While AvantGen received an upfront payment and is eligible to receive milestone and royalty payments.

The companies believe that their candidate in its original IgG format has shown potent neutralization activity in in vitro assays and in an in vivo animal model. This will have an advantage over the multiple vaccines that have been getting EUA, which are not suitable for immunocompromised patients. 

BeiGene, Novartis partner to develop cancer drug Tislelizumab, an Anti-PD-1 Antibody 

BeiGene has announced the collaboration with Novartis Pharma AG to develop, manufacture, and commercialize BeiGene’s anti-PD-1 antibody tislelizumab in the United States, Canada, Mexico, member countries of the European Union, United Kingdom, Norway, Switzerland, Iceland, Liechtenstein, Russia, and Japan. 

Already in markets in China, BeiGene’s Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages. It is approved for classical Hodgkin’s lymphoma (cHL) following at least two prior therapies and locally advanced or metastatic urothelial carcinoma (UC) with PD-L1 high expression. 

The duo will jointly develop the therapy, conducting clinical trials globally. BeiGene is eligible to receive an upfront cash payment of USD 650 million, up to USD 1.3 billion upon achieving regulatory milestones, USD 250 million for sales milestones, and royalties on future sales of tislelizumab in the licensed territory. At the same time, Novartis will take care of regulatory submissions after a transition period and for commercialization upon regulatory approvals. Besides, BeiGene has an option to co-detail the product in North America, which will be funded in part by Novartis.

Valo Raises USD 190 Million in Series B Financing and Unveils Select Therapeutic Programs

Valo has announced the closing of a USD 190 million Series B financing and unveiled select therapeutic programs. The company is creating a new systemic approach for drug discovery and development. The proceeds from Series B will continue to support the discovery and development of therapeutic programs that the company is undertaking. Further, Valo plans to use the sum to advance its proprietary Opal Computational Platform and its build working capital. 

The company plans to combine its unique human-centric dataset (over 125-million patient-years) with its Opal Computational PlatformTM with an aim to leverage machine learning and patient data for the facilitated and speedy development of products at clinical stages. Some of the key preclinical programs that Valo proudly owns include NAMPT, PARP1, USP28, and HDAC3. 

The financing was led by The Public Sector Pension Investment Board (PSP Investments), along with Valo’s existing major investors, including Flagship Pioneering and several new institutional investors, including Invus Public Equities, HBM Healthcare Investments, Atinum Investment, and Mirae Asset Capital.  

Bluebird spins off to two companies, cleaving off its gene therapy, and cancer units

Bluebird bio recently announced its plans to split its genetic disease and oncology businesses. The company has decided to prioritize its severe genetic disease unit and form its oncology business into a new company.

The decision came after the company struggled to commercialize its gene therapies, and as a result, its stocks continue to stumble down. Recently, bluebird bio decided against filing for USFDA approval for its gene therapy for sickle cell disease (SCD) for at least a minimum of 2 years. 

Another of its therapy, bb1111, a LentiGlobin treatment for SCD, was building its submission on promising data from Group C pf the HGB-206 study. The company and the agency had reached an agreement on a path to transition to commercial manufacturing using an analytical comparability strategy, including a suspension-based lentiviral vector (sLVV).

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Rocket Pharmaceuticals in orbit after gene therapy read-out

Shares in Rocket Pharmaceuticals have been living up to their name, shooting up following encouraging early-stage clinical trial results from a gene therapy for a serious inherited rare heart disease.

Results came from a phase 1 trial of RP-A501 for treatment of Danon Disease and sent shares up 75% on the Nasdaq to more than $56, a five-year high.

The surging stock price indicates the market’s confidence in gene therapy products after the successful launch of products such as Roche/Spark Therapeutics’ Luxturna, a gene therapy for a rare inherited eye disease.

Danon Disease is a rare X-linked disorder caused by genetic mutations in the LAMP2 gene and the therapy works by instructing the body to express a healthy copy of the LAMP2B protein in order to correct the condition.

The disease that affects boys and men more severely causes accumulation of autophagosomes – tiny structures that cause cells’ internal structures to break down – in the heart muscle and other tissues.

Together with a build-up of glycogen this can lead to severe and frequently fatal degradation of the heart muscle.

RP-A501 could be the first gene therapy for the disease and the early data showed a positive increase in cardiac protein expression.

As of November, three patients have been treated with a low dose of the therapy and two have been treated with a high dose.

An early trial readout showed two patients with LAMP2B expression that was 50% more than normal, measured nine and 12 months after treatment.

A 15%-20% increase could lead to clinically meaningful improvements in cardiac function and the trial reported a 50% decrease in a key biomarker of heart failure.

There was also a reduction in myocardial cell disarray and a visible reduction in autophagic vacuoles, a hallmark of the disease.

The company also noted stabilisation of three other measures – a heart failure biomarker known as BNP,  plus levels of transaminases and creatine kinase that also indicate skeletal and heart muscle damage.

However one patient who received the highest dose and had a degree of immunity to the adeno-associated virus used in the therapy had an immune reaction classified as a serious adverse event.

Rocket said the event was likely due to complement activation, resulting in reversible thrombocytopenia and acute kidney injury requiring a short round of haemodialysis.

The patient returned to baseline within three weeks and regained normal kidney function.

Dr Barry Greenberg, director of the Advanced Heart Failure Treatment Program at UC San Diego Health, Professor of Medicine at UC San Diego School of Medicine, and the principal investigator said: “Children with Danon Disease live with a heavy disease burden. Young boys are often severely afflicted.

“They show evidence of early onset skeletal muscle weakness and heart disease that can progress rapidly to end-stage with death occurring on the average before age 20. A heart transplant can be performed but is not curative and is associated with its own significant problems.

“The results-to-date for this first investigational gene therapy for monogenic heart failure show the potential for direct clinical benefit without emergence of unanticipated side effects of therapy.”

The company has also begun a stock offering of $175 million in shares to fund further development following the results.






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‘Knowledge is power’ for rare diseases and NAbs

Cure Rare Disease’s Rich Horgan discusses the importance of preclinical NAbs screening and helping rare disease patients better understand their eligibility for gene therapies.

Neutralising antibodies (NAbs) present a unique challenge to researchers looking to treat patients with AAV treatment. As AAV is a virus derived from the common cold, the immune system can easily have levels of pre-existing NAbs that will recognise and neutralise AAV, rendering it ineffective.

In serious cases, higher levels of pre-existing NAbs can even cause a dangerous immune reaction when such therapies are administered.

This is particularly pertinent in rare diseases, as a number of gene therapy products use viral delivery methods to deliver the transgene to target organs.

“NAbs are antibodies that are part of the humoral response of the adaptive immune system,” explains Rich Horgan, founder and president of Cure Rare Disease (CRD), a nonprofit biotech developing CRISPR therapeutics for Duchenne muscular dystrophy (DMD). “They defend against foreign pathogens or infectious particles, and are specific to the targeted antigen, neutralising its effect and rendering it no longer pathogenic by binding to it.

“The goal is to not have the body neutralise the therapeutic, and therein lies the issue with NAbs. For gene therapy treatments using viral delivery methods such as AAV, NAbs are an issue that we must all contend with for both initial patient dosing as well as subsequent redosing.

“Our belief is that patients should understand the challenges associated with drug development and how those challenges impact them personally… It is emotionally challenging for patients who must put their faith in the hands of pharma companies”

“Regardless of route of administration, the virus can be identified as a foreign pathogen causing the adaptive immune system to try and eliminate it through NAbs or other means.”

A further issue is that patients can, and do, develop NAbs from environmental exposure. For example, since AAV is derived from a common virus, patients can develop NAbs against AAV from common colds or other infections – and ultimately, even low levels of antibodies can prevent successful transduction of a viral-based therapeutic.

Clinical trials will screen potential patients for NAbs against the delivery vector to understand the level of NAbs present in the patient (known as the titer level) before dosing them with the experimental drug – but there is currently no standardisation for measuring NAb titer levels in a patient, and each pharma company develops their own assay for testing.

“Moreover, there is not a generally agreed upon threshold for a dose/no-dose decision,” says Horgan. “Ultimately, titer levels are related to safety, as dosing a patient who has a higher titer level (however that may be defined) is more likely to trigger an immune response to the treatment, an extreme example being the infamous case of Jesse Gelsinger.

“As additional gene therapy trials advance, it is important that bodies like the FDA begin to standardise NAb measurement assays and acceptable titer levels for inclusion in clinical trials.”

But although companies are able to screen patients in an attempt to avoid complications, only those already in line for clinical studies qualify, even though for many patients it’s critical to know this information in advance as they consider potential trials.

“To date, there hasn’t been a widely available mechanism for patients and patient families to get insight into whether or not they have a significant level of NAb activity other than through enrollment in a clinical trial,” says Horgan.

Because of this, Horgan believes there needs to be more conversations surrounding this issue, and much more education of patient communities regarding the issue of NAbs and the challenges they create towards participation in a gene therapy study.

“Our belief is that patients should understand the broad challenges associated with drug development and how those challenges may impact them personally. While drug development is technically challenging, it is even more emotionally challenging for patients and patient families who must put their faith in the hands of pharma companies to develop effective treatments for their disease.

“Given the rise of many gene therapies, especially those in the rare disease space, neutralising antibodies stand as a significant challenge to the patient community and it is critical that patients understand that a) these neutralising antibodies exist and can potentially prevent patients from participating in a gene therapy clinical trial and b) collaborative development efforts are needed to ensure that patients can get access to life-saving gene therapies if they possess a significant level of NAbs.”

As such, CRD has rolled out a new system to allow patients to get an understanding of where their neutralising antibody levels stand – knowing that these levels may change over time and that medical decisions should not be based on these results.

The system offers community access to preclinical neutralising antibodies screening. CRD enrolls patients into their research study, then sends a patient kit for local blood collection through a lab. Patients are then informed of the research results several weeks later, and are provided genetic counselling to understand and emotionally handle the results.

“We’ve gone to great lengths to provide a high level of counselling as we know, from personal experience, the results are more than data points – they are the hopes and dreams of a family counting on a potentially life-saving gene therapy,” says Horgan.

“Ultimately, we believe that patients should have knowledge of the impact of neutralising antibodies and must advocate for the advancement of technologies so that all patients may be eligible for viral-based therapeutics. Time and access are of the essence.”

Horgan says that the long-term benefits for families who choose to get screened comes from this generated knowledge.

“Knowledge is power. While the information provided does not change the reality of the situation, we hope that it encourages families to ask more questions and to advocate for the development of technologies to enable dosing with a viral-based therapeutic.

“While non-viral gene therapies will someday be possible, leading researchers believe it will be a number of years before this is realistically feasible.

“Moreover, we want to help patients avoid the immense emotional disappointment of a situation where the patient is found to be ineligible for a gene therapy study due to NAbs even though they never knew that NAbs were an issue to begin with.

“By rallying together a community, we can catalyse the development of technologies to enable dosing (and re-dosing) of advanced therapeutics so that all have access.”

About the interviewee

Rich Horgan is the founder and president of Cure Rare Disease. He has a deep passion for Duchenne muscular dystrophy (DMD) and other rare diseases. With a younger brother impacted by DMD, Rich has a strong interest in accelerating promising treatments for the disease. He has formed a collaboration with world-class researchers and clinicians to pioneer the rapid development of customised therapies for Duchenne and other rare diseases.

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2nd Gene Therapy for Blood Disorders

2020 has been an exciting year for gene therapies targeting blood disorders. Despite FDA’s recent rejection of BioMarin’s hemophilia gene therapy program, the clinical landscape is progressing quickly with Pfizer and Sangamo kicking off their phase 3 and bluebird bio receiving European approval for their beta-thalassemia candidate.

With pipelines advancing and emerging companies joining the blood disorders field, it is essential for gene therapy developers to communicate and share lessons learned to accelerate their programs to market. The 2nd Gene Therapy for Blood Disorders meeting is taking place in March 2021, focusing on the clinical and commercial challenges of developing gene therapies targeting hemophilia, sickle cell disease and beta thalassemia.

Evaluate the best strategies for a commercial launch in blood disease and optimize your trial design to ultimately transform your clinical candidates into a commercial reality.

Download the full event guide to learn more from companies including bluebird bio, Spark Therapeutics and Editas Medicine.

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Gene Therapy Medical Affairs

The inaugural Gene Therapy Medical Affairs Summit is dedicated to exploring the pivotal internal and external role that Medical Affairs plays in delivering gene therapies to patients.

Industry pioneers from leading pharma and biotech companies at various stages of development and commercialization including Novartis Gene TherapyOrchard Therapeutics & Bluebird Bio will share how to engage effectively with internal clinical and commercial teams as well as external HCPs, regulators and patient advocates to create a cohesive and streamlined launch strategy for complex, high priced gene therapy products and ultimately work to remove both barriers that exist for access to gene therapies.

Join this definitive, niche conference to delve into the unique Medical Affairs challenges encountered when working with gene therapies, from adapting to the clinical realities of the rare disease space to handling long-term follow up and post-launch scrutiny, equipping you with the insights required to launch gene therapy products more efficiently and effectively than ever before.

This virtual event is set to be a highly interactive and engaging meeting. We fully understand (and quite frankly agree) that a presentation-heavy conference just isn’t up to scratch! As such we have created a new format for this meeting which maximises opportunities for engagement, discussion, and Q&A’s in order for you to get the best value from this meeting.

Access the official agenda for more information.

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Helixmith starts new trial of diabetic neuropathy gene therapy

Just over a year after its first phase 3 trial of its Engensis gene therapy for painful diabetic peripheral neuropathy (DPN) bombed, Helixmith has started dosing patients in a new study.

The South Korean biotech says the DNA plasmid-based therapy has been administered to a patient at Innovative Research of West Florida. The aim is to enrol 152 DPN patients at 15 clinical sites across the US in the study, called REGAiN-1A.

Helixmith has previously suggested that if positive, the new study could support marketing applications for Engensis. It is due to generate results in December 2021, which could lead to filings in 2022.

While most gene therapies in late-stage development target rare diseases, DPN is a relatively common condition and is likely to become even more prevalent as diabetes is becoming more common around the world. It has a lifetime prevalence of around 50% in people with diabetes, with around half of these having pain.

In DPN, prolonged exposure to higher than normal blood sugar levels damages nerves, most commonly in the legs and feet but also in the arms and hands.

At the moment treatment is limited to drugs like gabapentin and pregabalin, which are only palliative and don’t tackle the underlying cause of the condition.

Engensis – also known as VM202 – is a DNA plasmid-based gene therapy that is administered as an intramuscular injection into the calves, delivering a gene coding for human hepatocyte growth factor (HGF).

The hope is that delivery of Engensis to the lower limbs might promote nerve system regeneration and alleviate the pain that often accompanies DPN, whilst also promoting blood vessel growth in the extremities.

In its first 500-patient phase 3 trial, called DPN 3-1, Engensis was no better than placebo at reducing pain scores over the first 90 days of the trial. However Helixmith (formerly known as ViroMed) said that was due to a major mix-up in the study protocol, which undermined the results.

Analysis of samples taken from patients in the placebo group found traces of the VM202 plasmid, suggesting that clinicians may have inadvertently administered the gene therapy to the control group.

There was also a wide variation in the amount of plasmid DNA among the treatment group, which might suggest inaccuracies in the administration of the gene therapy. On the plus side, safety results were in keeping with a benign profile seen in earlier-stage clinical trials.

Helixmith then started a phase 3 extension study in 101 subjects from DPN 3-1 – conducted under a separate protocol – to look at long-term safety and efficacy at 12 months.

That backed up the safety data for the therapy, and also found significant pain reductions compared to placebo after six, nine and 12 months, as well as a trend towards reduced pain at three months.

The primary measure in REGAiN-1A  will be a comparison of the average daily pain scores from seven days prior to the first injection, to seven days prior to the six-month visit between both the Engensis and placebo groups.

Secondary efficacy measures include pain reduction at six months compared to placebo, as well as the proportion of patients experiencing a 50% reduction in pain at six months. The therapy will be administered by injection into the calf at day zero, 14, 90 and 104.

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UCB Acquires Handl Therapeutics to Augment its Gene Therapy Portfolio


  • The acquisition will bolster UCB’s pipeline program, capabilities, and platforms in the gene therapy space. The Handl Therapeutics will continue to be based in Leuven, Belgium while working closely with UCB’s international research teams
  • In addition, the UCB collaborated with Lacerta to focus on CNS diseases, under which Lacera will lead research, preclinical activities, and the early manufacturing process development, while UCB will complete IND-enabling studies, manufacturing, and clinical development
  • The collaboration will allow UCB to access Lacerta’s expertise in AAV-based CNS targeted gene therapies, fortifying UCB’s ability to produce effective treatments for neurodegenerative diseases

Click here­ to­ read full press release/ article | Ref: PRNewswire | Image: The Pharma Letter

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UCB revs up its gene therapy drive with Handl acquisition

UCB has made a new foray into the gene therapy space, buying fellow Belgium-based company Handl to get control of its adeno-associated virus (AAV) capsid delivery platform and two research programmes in neurodegenerative diseases.

The mid-sized pharma group has also signed a collaboration with Florida, US-based Lacerta Therapeutics, adding more AAV capsids – well established as a staple for delivering gene therapy sequences – as well as another gene therapy candidate.

Like many other pharma companies, UCB has been building a presence in gene therapy as the sector gathers momentum with more therapies getting regulatory approval.

The company says that is part of a shifting focus from “symptomatic treatments to disease modification and eventually towards a cure.”

In 2018, it bought Element Genomics – a spin-out of Duke University in the US – to add genome-editing technologies, and has also been growing its internal exercise at its Boston R&D hub, although so far it hasn’t advanced and gene therapies into clinical development.

Earlier this year, UCB also bought a 47-acre UK R&D campus from Eli Lilly, saying it intends to develop it as a hub for R&D in “gene therapies, translational medicine and antibody discovery.”

It is also in the process of constructing a €300 million biological manufacturing facility at its site in Braine l’Alleud, Belgium, to ensure the supply of medicines in clinical development.

“A vast array of diseases are amenable to gene therapy and UCB is embracing this modality to expand its capabilities and ultimately transform the lives of patients with severe diseases,” said the company in a statement.

It added that AAV-mediated gene therapy can “drive a fundamental change in how diseases are treated with the ability to remove or add disease-related proteins with a single treatment.”

Leuven-based Handl was formed last year by Prof Michael Linden – formerly vice president of gene therapy at Pfizer – and Florent Gros, who has held executive positions at Nestlé, Pasteur Merieux Connaught and Novartis.

Handl’s technology portfolio stems from licensing deals with Prof Linden’s former employer King’s College London, as well as Belgium’s KU Leuven, the Centre for Applied Medical Research in Spain, and the University of Chile.

UCB hasn’t revealed how much it is paying for Handl, or indeed the terms of its alliance with Lacerta, a University of Florida spin-out which also focuses on central nervous system diseases and will contribute research and manufacturing expertise.

Handl has also tapped into the development and manufacturing capabilities at Novasep, a contract manufacturing organisation (CMO) also based in Belgium.

Under the terms of that agreement, Novasep will develop and manufacture AAV vectors and supply drug substances to support Handl’s preclinical and clinical studies.

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Novartis keeps a close eye on gene therapy with Vedere Bio buy

Already a major player in gene therapy, Novartis has swooped on US startup Vedere Bio in a $280 million deal that builds its position in inherited eye diseases that can lead to blindness.

Incubated by Atlas Ventures, Cambridge, Massachusetts Vedere has been flying under the radar since it was founded in 2019 to develop adeno-associated virus (AAV) based gene therapies for ocular diseases, but didn’t escape the beady eye of Novartis.

The Swiss pharma group already sells one gene therapy for inherited retinal diseases (IRDs) – Luxturna (voretigene neparvovec) – for which it licensed ex-US rights from Spark Therapeutics (now part of Roche) in 2018.

Novartis’ big move in the gene therapy market came when it bought AveXis for $8.7 billion in the same year to add spinal muscular atrophy therapy Zolgensma (onasemnogene abeparvovec), which has made $1 billion in sales since launch last year.

Earlier this year, the group also signed a licensing deal with Dyno Therapeutics for its AAV capsid-based gene delivery technology, also focused on ocular disease which remains one of Novartis’ core drug development targets despite the spin-off of the Alcon eyecare division in 2019.

Shortly after, Novartis teamed up with Sangamo in a deal focused on the adjacent gene therapy discipline of gene silencing, targeting neurodevelopmental disorders like autism.

The Vedere acquisition includes $150 million upfront and $130 million in potential milestones, and expands Novartis position in ocular disease gene therapy with an AAV delivery platform as well as rights to light-sensing proteins that can be delivered to cells in the retina.

It also gets two preclinical-stage development projects. One focusing on IRDs – a wide range of genetic retinal disorders caused by mutations in some 250 genes that are marked by the loss of photoreceptor cells and progressive vision loss. IRDs affect around 2 million people worldwide.

The second is looking at geographic atrophy, an advanced form of ‘dry’ age-related macular degeneration (AMD) that affects around 5 million people around the world and has no approved medical treatments.

While gene therapies like Luxturna are aimed at preventing progressive vision loss, Novartis thinks it could go a step further with the Vedere platform and attempt to restore vision that has already been lost – something that the company’s scientific founders have achieved in animal models.

Combining the light-sensing proteins and AAV platform has the potential “to vastly expand the number of patients who could be treated for vision loss due to photoreceptor death,” according to the company.

When delivered to retinal cells, the proteins stimulate them to sense and transmit information to the visual processing centres in the brain, bypassing cells that have already degenerated.

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Bayer buys cell & gene therapy firm AskBio for $4 billion

Bayer is making clear its ambitions in cell and gene therapy with a $4 billion acquisition of US biotech Asklepios BioPharmaceutical, also known as AskBio.

AskBio’s portfolio includes pre-clinical and clinical stage candidates for the treatment of neuromuscular, central nervous system, cardiovascular and metabolic diseases.

Through the acquisition, Bayer will gain full rights to the company’s gene therapy technology and manufacturing platforms, including AskBio’s adeno-associated virus (AAV)-based platform, which has already demonstrated applicability across different therapeutic areas. 

The company’s most advanced programmes are in Pompe disease – a rare genetic disease causing buildup of a sugar molecule inside cells – Parkinson’s disease and congestive heart failure.

Under the terms of the agreement, Bayer will pay $2 billion, with a further $2 billion marked out for potential success-based milestone payments.

According to the company’s statement, some 75% of the potential success-based milestone payments are expected to be due during the course of the next five years and the remaining amount late thereafter.

Last year Bayer fully acquired another cell therapy company, BlueRock Therapeutics – which was created in 2016 via a joint venture between Bayer and Versant Ventures, and is also working on Parkinson’s Disease therapies. 

Like with BlueRock, Bayer says it wants AskBio to operate on an “arm’s-length basis” to “persevere its entrepreneurial culture as an essential pillar for nurturing successful innovation”.

Reuters reports that AskBio and BlueRock will exchange information and collaborate but will each operate as independent companies. In light of this, AskBio’s five main owners have pledged to remain with the firm.

“We are staying on board because of the unique structure that Bayer has provided,”  said CEO and co-founder Sheila Mikhail.  We’ll have the ability to make our science decisions.”

Cell and gene therapy is viewed as one of the most promising areas in pharma, with several biotech and big pharma firms making plays in the area.

These therapies offer new treatment options for many currently untreatable diseases, particularly genetic diseases caused by a single genetic defect.

AskBio has licensed some of its experimental drugs to external partners, such as Pfizer, which recently won fast-track designation in the US for a Duchenne Muscular Dystrophy candidate, PF-06939926, that was invented by AskBio.

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Cleveland Clinic Names Top 10 Medical Innovations For 2021

Cleveland Clinic Names Top 10 Medical Innovations For 2021

Cleveland Clinic’s top clinicians and researchers present the top 10 medical innovations transforming medical advancements and new awards to recognize healthcare innovation.

The list of breakthrough technologies was selected by a committee of Cleveland Clinic subject matter experts, led by Will Morris, M.D., executive medical director for Cleveland Clinic Innovations, and Akhil Saklecha, M.D., managing director of Cleveland Clinic Ventures.

Here is a look at the top 10 medical innovations for 2021 with the power to transform healthcare in the next year:

1. Gene Therapy for Hemoglobinopathies

2. Novel Drug for Primary-Progressive Multiple Sclerosis

3. Smartphone-Connected Pacemaker Devices

4. New Medication for Cystic Fibrosis   

5. Universal Hepatitis C Treatment   

6. Bubble CPAP for Increased Lung Function in Premature Babies   

7. Increased Access to Telemedicine through Novel Practice and Policy Changes  

8. Vacuum-Induced Uterine Tamponade Device for Postpartum Hemorrhage   

9. PARP Inhibitors for Prostate Cancer   

10. Immunologics for Migraine Prophylaxis   

Axovant pushes on with Parkinson’s gene therapy, despite investor cynicism

Axovant has said it plans to continue developing its Parkinson’s Disease gene therapy after reporting supportive data from a small cohort of patients from a phase 2 trial.

However shares in Axovant were down sharply after the announcement because of market sentiment that the New York biotech had been selective with the data it had shared in its update.

The data came from a second cohort of just four patients in the phase 2 clinical trial SUNRISE-PD, although the improvement in symptoms was dramatic.

Chief R&D officer Gavin Corcoran said that the therapy known as AXO-Lenti-PD could transform treatment of patients with Parkinson’s through a one-time shot of gene therapy.

The company plans to begin EXPLORE-PD, a randomised, sham-controlled study next year, which will evaluate safety and tolerability at higher volumes of infusion.

Latest results showed that in two evaluable patients in the cohort, there was a 21-point mean improvement in a score measuring motor function during “off” periods, a 40% improvement from the baseline average score of 52 in these patients.

There was also evidence of dose response when compared with results at lower doses.

However the company said that COVID-19 and a patient refusal in the cohort at UK trial sites meant that two of the patients could not be scored at the six-month follow-up.

All four subjects were able to complete all other efficacy assessments at six months, including the patient-recorded symptom diaries.

Axovant is working with sites and investigators to ensure safe and ethical data collection at future time points through the pandemic in accordance with regulatory guidance.

It added that the gene therapy was generally well-tolerated in four patients receiving gene therapy, with no serious adverse events at six months after a single administration in the four subjects.

The subjects had an average age of 57 years and an average duration of Parkinson’s disease of 13 years, the company said.

In patients with PD specialised neurons in the brain producing the neurotransmitter dopamine die and the patient’s movements become erratic and uncontrolled, progressively declining over time.

Parkinson’s is not a true genetic disease, although certain genes have been linked to an increased likelihood of onset.

But Axovant is using a gene therapy approach to treat the disease – Axo-Lenti-PD works by turning other neurons in the brain into dopamine factories to replace those lost as the disease progresses.

The company hopes that by taking this approach it will solve the problem of “off” periods that occur with conventional therapies.

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EMA starts rapid review of Bluebird’s gene therapy for rare disease CALD

Bluebird bio could be just a few months away from approval of its gene therapy for rare disease cerebral adrenoleukodystrophy (CALD) in the EU, after the EMA started an accelerated review.

If approved, Lenti-D (elivaldogene autotemcel or eli-cel) could transform the prospects of people with CALD, the most severe form of the neurodegenerative disease ALD that usually emerges in boys during early childhood and causes physical and mental disabilities as well as behavioural problems.

Around 40% of patients develop the cerebral form of ALD, which in turn affects around one in 17,000 live births.

A few weeks ago, Bluebird reported new data from the phase 2/3 STARBEAM trial of Lenti-D which showed that 87% of CALD patients were still alive and free of major functional disabilities after at least two years’ follow-up.

The EU filing comes ahead of a filing for eli-cel in the US, which Bluebird says should take place sometime towards the middle of next year, having been delayed by the coronavirus pandemic.

If approved, eli-cel would provide a one-shot treatment for CALD, holding back the progressive breakdown in the protective myelin that sheathes neurons.

It would be the first alternative to a stem cell transplant to treat the disease, a therapy that can provide significant improvements and even halt progression in some patients if given early enough.

However it requires high-dose chemotherapy to destroy the bone marrow, and that poses significant risks to patients in its own right, and can also lead to graft-versus-host disease, a potentially life-threatening complication in which the bone marrow donor’s immune cells attack the recipient’s cells and tissues.

CALD is caused by mutations in the ABCD1 gene located on the X chromosome, which provides instructions for the production of the ALD protein.

ALD protein is needed to clear toxic molecules called very long-chain fatty acids (VLCFAs) in the brain, and if mutated causes the VLCFAs to accumulate and damage the myelin sheath.

Using eli-cel, the patient’s own stem cells are modified in the lab to produce a working version of the ABCD1 gene, producing functional ALD protein that can help to flush VLCFAs from the body.

“CALD is a devastating disease, often marked by rapid neurodegeneration, the development of major functional disabilities, and eventual death,” said Gary Fortin, head of severe genetic disease programmes at Bluebird.

“If approved, eli-cel would represent the first therapy for CALD that uses a patient’s own haematopoietic stem cells, potentially mitigating the risk of life-threatening immune complications associated with transplant using cells from a donor,” he added.

Aside from STARBEAM, which will follow treated patients for up to 15 years, Bluebird is also conducting the phase 3 ALD-104 trial of eli-cel in CALD, which is due to generate results in 2024.

The EU filing for eli-cel comes shortly after Bluebird’s development partner received a 27 March 2021 FDA review date for anti-BCMA CAR-T cell therapy ide-cel, a potential therapy for multiple myeloma.

The biotech already has approval in Europe for Zynteglo, a gene therapy for haematological disease beta thalassaemia, and is due to file its related therapy LentiGlobin for sickle cell disease next year. The two therapies have been tipped to generate $1.5 billion-plus in peak sales by some analysts.

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Astellas’ Audentes Therapeutics discloses third patient death in gene therapy trial

dna, genomics

The clinical trial had already been placed on hold in connection with the two prior patient deaths, which were linked to the higher dose of 300 trillion viral vectors per kilogram, while no deaths have been reported among those receiving the lower dose of 100 trillion vectors.

FDA rejects BioMarin’s hemophilia A gene therapy in ‘massive surprise’

In a CRL issued for valoctocogene roxaparvovec, the FDA told BioMarin that differences between its Phase I/II and Phase III studies limited the ability to rely on the earlier trial to support durability of effect, which an analyst said likely referred to a product comparability issue.

Preparing for an influx of cell and gene therapy approvals

Cell and gene therapies offer some of the most groundbreaking advancements in patient care the pharma industry has ever seen. However, to fully realise the potential of these innovative therapies, integration across the supply chain is critical – particularly with reimbursement and logistics.

As of the end of 2019, there were 17 cell and gene therapy products approved by the FDA. Now, there is more momentum than ever to bring these innovative medicines to market, and the FDA anticipates that it will approve 10 to 20 cell and gene therapy products a year within the next five years.

These therapies can offer new opportunities to patients with conditions where there are few treatment options and no cures. But the potential these products offer could remain largely unrealised if manufacturers and their partners are not prepared. Cell and gene therapy innovators and other stakeholders across the supply chain need to set themselves up for the greatest chance of success by addressing three key challenges: access barriers; logistics; and the need for stakeholder education.

Addressing access barriers through innovative payment models

While cell and gene therapies offer novel treatment to patients who have limited options, the cost associated with each product – anywhere between $375,000 and $2 million – can create significant access barriers. This challenge is compounded compared to traditional treatments that typically require multiple doses, as many cell and gene therapies are one-time treatments.

This situation increases the risk for payers covering the cell and gene therapy, given that the long-term magnitude and durability of the product is not known at the time of first regulatory approval and patients switch insurance carriers throughout their lifetimes.

“Stakeholders across the industry have recognised the increasing need to consider alternatives to the standard payment system if cell and gene therapies are to become widely available”

Stakeholders across the industry, such as manufacturers and payers, have recognised the increasing need to consider alternatives to the standard payment system if cell and gene therapies are to become widely available. As a result, a variety of payment models have been discussed:

  • Value-based model: The payer pays only a portion of the full price upfront. If the therapy achieves prespecified outcomes, the payer remits the remainder in full. This model spreads the financial risk, therefore, between the payer and manufacturer, and has been the most commonly employed method to date.
  • Pay-over-time model: The payer agrees to a fixed price for the therapy but pays in regular installments, like with an annuity, spreading the cost over time.
  • Subscription-based model: This model offers the payer a flat rate for coverage of various cell and gene therapy products, which provides predictability and helps them offset the potentially high upfront costs of these therapies and realise longer-term cost-savings.

We have already begun to see payers and manufacturers of cell and gene therapies attempt to adopt alternative payment models for their products, and more should continue to do so as additional therapies come through the approval pipeline. With a range of interdependencies that affect the success of cell and gene therapies, manufacturers need to develop their reimbursement strategy early in the commercialisation process. It’s critical for manufacturers to consider various payment models for cell and gene therapies ahead of approvals so that they can maximise patient access for their products.

Ensuring therapies reach their patients

Manufacturers have noted that the delivery of critical shipments is one of the biggest challenges facing the advanced therapy industry, as if you cannot connect cell and gene therapies with patients their efficacy is irrelevant. The inclusion of patients into the cell and gene therapy supply chain, the potentially life-altering impact of the therapies and their high cost leaves no room for failure.

These therapies require timely delivery and maintaining precise temperature control is integral for the patient and the product. It calls for near-perfect execution ranging from mapping the best transportation route and planning for multiple contingencies (such as closed international borders), to how the packaging itself is evaluated, validated and used to maintain product integrity in all conditions.

Successful execution of these processes requires both manufacturers and other supply chain partners to maintain a robust logistics platform. Currently, many manufacturers are developing different logistics plans for each of the stages of a clinical trial, only to find out these processes don’t scale when it is time to commercialise. Developing a plan early that can scale will position a product for success as more therapies are reviewed and approved. Manufacturers need to work with their 3PL and distribution partners to ensure control and oversight throughout the product journey to the patient – failure to do so will put patient outcomes and commercial success at risk.

Promoting stakeholder education

Many stakeholders – spanning payers, providers and patients – do not understand the full clinical, logistical, operational, financial or reimbursement components associated with cell and gene therapies. Manufacturers can leverage the preliminary data they’ve gathered throughout their initial commercialisation journey to support education and awareness efforts with these key stakeholders.

As payers conduct product reviews earlier and earlier in the development lifecycle, their demand for pre-approval information continues to grow. However, recent research shows that a gap still exists between the evidence sought by healthcare decision makers and what is being shared by manufacturers. COVID-19 has also caused delays in providing information in a timely and relevant manner, causing even more challenges for stakeholders.

The use of Pre-approval Information Exchange (PIE) is one way to combat these challenges. PIE allows manufacturers to communicate ahead of approval to partners with accurate, and unbiased information on products or indications, and share information early that may result in a “place saved at the table” for their product. This information equips stakeholders with the education needed to understand a product’s value story and positioning. Partners embedded in the industry – particularly those with a patient-centric focus – can also offer manufacturers the information they need to showcase the value of these products to patients.

The cell and gene therapy space is continuing to evolve. Through analysing payment models, working with partners to navigate logistical challenges and leveraging data, patients will have more opportunities than ever to access the next generation of medicines. Overall, the collaboration between stakeholders across the supply chain will facilitate a world in which we see 10 to 20 cell and gene therapies not only approved each year but out in the market directly impacting patients.

About the authors

Alex Guite is vice president services and alliances at World Courier. As strategy and services lead, Alex is responsible for developing and executing key strategic initiatives.Before joining World Courier in 2013 as head of pricing, Alex spent nearly 3 years with Oliver Wyman as a consultant in the Health and Life Sciences practice.

Ana Stojanovska is vice president, reimbursement & policy insights at Xcenda. She has extensive practical knowledge in working with key stakeholders to motivate local coverage of new products by both public and private payers and providing strategic compendia analyses and ongoing coding support. Prior to Xcenda, Ana worked for a bipartisan, non-profit health policy organization in Washington DC, where she helped lead research, health policy analysis, media outreach, and fundraising.

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Kite’s Tecartus (brexucabtagene autoleucel) Receives the US FDA’s Approval as the First Cell-Based Gene Therapy for Relapsed or Refractory MCL


  • The accelerated approval follows FDA’s PR and BT designation and is based on ZUMA-2 study assessing Tecartus (formerly KTE-X19) in 74 patients with r/r MCL prior treated with  anthracycline/ bendamustine-containing CT, an anti-CD20 Ab therapy and a BTK inhibitor (ibrutinib or acalabrutinib)
  • Results: 87% patients responded to Tecartus (single infusion), including 62 % patients achieved CR, 18% experienced Grade 3 or higher CRS and 37% experienced Grade 3 or higher neurologic toxicities
  • Tecartus is an autologous, anti-CD19 CAR T cell therapy, currently under EC review and has received EMA’s PRIME designation for r/r MCL. The therapy will be manufactured in Kite’s commercial manufacturing facility in El Segundo, California

Click here to read full press release/ article | Ref: Kite | Image:  Stat News

Biogen plans trial of Spinraza in patients not responding to SMA gene therapy

Biogen is planning to trial its Spinraza spinal muscular atrophy (SMA) drug in patients who have not responded properly to Novartis’ gene therapy Zolgensma, combining the two ultra-expensive therapies to treat the rare muscle-wasting disease.

In the US, a single shot of Zolgensma (onasemnogene abeparvovec) costs $2.1 million, while Spinraza (nusinersen) costs $750,000 in its first year.

Biogen said it aims to begin a phase IV study as in a long-term follow-up study of Novartis’ drug it has been reported that some patients have been subsequently treated with Spinraza.

The phase IV RESPOND study aims to test efficacy and safety of Spinraza with a suboptimal clinical response to Zolgensma.

So far four out of 10 patients in a long-term study of Zolgensma have been subsequently treated with Spinraza, Biogen said.

Based on the planned study design, RESPOND will be a two-year, open-label study to evaluate the efficacy and safety of Spinraza in SMA patients previously treated with Zolgensma to further inform treatment decisions.

Efficacy will be assessed by change from baseline on motor function measures and additional clinical outcomes such as swallowing and caregiver burden.

Neurofilament levels, an exploratory endpoint, will also be evaluated as a marker of biological disease activity.

The primary study group aims to include 40 infants aged nine months or younger at the time of the first dose of Spinraza, who have two copies of SMN and are likely to develop type 1 disease and received Zolgensma at six months old or younger.

A second study group will include 20 children and will generate data in patients with a broader age range, up to three years old at the time of the first Spinraza dose.

After a screening period, participants will receive the approved 12 mg dose of Spinraza, which is four loading doses followed by maintenance doses every four months, over the two-year study period.

If approved by regulators the company aims to begin enroling patients in the first quarter of next year.

While Zolgensma is a gene therapy that aims to correct the genetic defect that causes the disease, Spinraza works by increasing the amount of full-length SMS protein that is critical to maintaining motor neurons.

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Pandemic hits sales at Novartis after strong launch for SMA gene therapy

The COVID-19 pandemic has bit into sales at Novartis, the big Swiss pharma said in second quarter results, after orders fell back following a period of stockpiling earlier in the year.

Figures for the quarter showed reported sales fell by 4% to $11.3 billion compared with the corresponding period last year, although favourable currency fluctuations helped to soften the impact.

Net income was a reported $1.9 billion, down 11% compared with last year’s Q2.

The company said that COVID-19 negatively affected sales in April and May, mainly because of fewer patients starting courses of medicine and reducing visits to the doctor.

Novartis added that digital technology and new ways of working are helping to keep the company running smoothly and have reduced costs.

It has a digital clinical trial management system that has allowed trials to continue despite the disruption caused by the coronavirus outbreak.

The company said measures had “limited COVID-related impacts” to trial data filing timelines.

Results also showed a strong launch for its rare diseases gene therapy, Zolgensma, which is now approved for the muscle wasting disease spinal muscular atrophy (SMA) in the US and EU.

Zolgensma is a one-off shot that corrects the underlying genetic cause of the disease and is notable for being the world’s most expensive drug at $2.1 million.

Novartis’ AveXis unit only began launches of the drug in Europe this month, a few weeks after the drug hit the market in Japan.

But sales in the US are going well, where payers are clearly finding ways to deal with the drug’s price tag.

In Q2 Zolgensma generated revenues of $205 million, and for the half year they were $375 million.

Novartis’ psoriasis drug Cosentyx continues to gain traction with sales increasing by 10% to $944m in Q2, but sales of multiple sclerosis pill Gilenya fell in a competitive market, down by 11% to $738 million.

There is also a potential threat of generic competition to Gilenya, although Novartis said its forecasts assume that there will be no US generic approved this year.

The company said that guidance has “tightened” within previously announced ranges – net sales are expected to grow mid single digit, with core operating income expected to grow low double digit.


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