A group of gene therapy experts called for better research tools and more careful monitoring of side effects to treatment, but stopped short in a high-profile meeting Thursday of advocating for major changes to how studies in the fast-growing field are conducted.

The committee, which the Food and Drug Administration convened for advice on the risks to gene therapy, proposed a number of ways research could potentially be made safer, such as by improving how patients are screened for clinical trials. None of the panel members, though, suggested slowing research in any significant fashion, rejecting, for instance, the idea of imposing an upper limit on gene therapy doses to lower risks.

"While the meeting was an excellent update on pre-clinical and clinical adverse events in the field, it largely left untouched what measures might actually be taken to help future-proof this field," said Anthony Davies, founder and CEO of Dark Horse Consulting, which specializes in gene therapy.

Experts said that inconsistent standards in how gene therapies are produced, and how certain safety risks are assessed, made it difficult to come up with recommendations that could be broadly applied.

The meeting, which will continue Friday, comes after a series of safety incidents in gene therapy clinical trials resurfaced some longstanding concerns, as well as new worries about the use of high treatment doses. The deaths last year of three children in a study of a neuromuscular disease therapy, in particular, appear to have spurred the FDA to seek the experts' advice.

"Our enthusiasm for this field must be balanced by caution," said Wilson Bryan, director of the FDA's Office of Tissues and Advanced Therapies, in a presentation opening the meeting Thursday. "The greatest risks in drug development fall on the patients who receive an investigational product."

The FDA split the first day of the meeting into two sessions, focusing the first on the persistent worry that injecting genes into cells might eventually spur cancer, and the second on the liver injury that can be caused by treatment. The committee will discuss brain toxicity Friday.

In discussing the risk of cancer, experts spent considerable time weighing findings from testing in animals, some of which dates back more than 20 years. Results have shown that a commonly used delivery tool, the adeno-associated virus or AAV, can fuse itself into the genomes of certain animals and, at least in mice, that integration is associated with liver cancer.

Concerns around whether this risk can play out similarly in humans grew earlier this year when a patient given an experimental hemophilia gene therapy developed by the biotech company UniQure was diagnosed with liver cancer.

UniQure has since exonerated its gene therapy, and experts at the FDA panel noted the risk remains theoretical. Other research in larger animals and in humans haven't replicated the worrisome findings in mice. A study following dogs given a hemophilia gene therapy and presented at the meeting by University of Pennsylvania researcher Denise Sabatino, for example, showed AAV did get into the genome but didn't lead to cancer.

"[T]his is something that will need to be monitored very carefully, [but] so far, the signal in the clinic doesn't seem to be very strong," said Christopher Breuer, the director of the center for regenerative medicine at Nationwide Children's Hospital, a top gene therapy hub.

Pfizer, which has invested heavily in gene therapy, argued companies shouldn't have to run more studies looking for integration events in animals until there is "clear causality in humans," according to a public comment filed with the FDA. Pfizer claimed additional experiments using human cell lines to assess risk would be more relevant.

FDA panelists, meanwhile, said longer animal tests might more effectively capture any cancer risk of AAV, as will tracking the health of the more than 800 children who have so far received the Novartis spinal muscular atrophy treatment Zolgensma. Experts also suggested closer scrutiny of gene therapy components.

But several were hesitant to make broad recommendations to the FDA as there aren't set rules for every aspect of how gene therapies are made.

"We are starting to get a sense of the scientific issues that are out there, but we need to start to drive towards some type of standardization," said Taby Ahsan, the head of biologics analytical development at MD Anderson Cancer Center. "Understanding that will help us give solid recommendations for preclinical study design as we move forward."

While the cancer risk of AAV gene therapy in humans remains theoretical, liver toxicity is one of the most common side effects reported in clinical testing to date and, in a few cases, has led to serious health problems.

In a study of a gene therapy developed by Audentes Therapeutics, for instance, three young children given a very high dose developed liver damage and later died, although the exact link between their deaths and the treatment is still unclear. Two cases of acute liver failure have also been reported in patients treated with Zolgensma, and many hemophilia patients across several gene therapy studies have experienced significant increases in liver enzyme counts, a potentially worrisome sign.

"I think that a lot of the studies have missed opportunities to involve hepatologists early on," said Theo Heller, a liver specialist at the National Institute of Diabetes and Digestive and Kidney Diseases, at the meeting. "Hepatotoxicity is such a common side effect of this therapy."

Experts did call on researchers to more comprehensively assess and screen for preexisting liver conditions, which they said might affect how side effects develop.

"We do need careful screening," said Lisa Butterfield, the meeting's chair and vice president of the Parker Institute for Cancer Immunotherapy at the University of California, San Francisco. "We need to focus on more than just fluctuations in blood work."

The committee made few other concrete recommendations on how best to manage the risk of liver problems, though. In particular, they opposed placing an upper limit on the gene therapy doses that could be tested, although research suggests the worst health consequences to liver toxicity only emerge at higher doses.

A major sticking point, some members noted, was the difficulty in characterizing the make-up of gene therapy doses, which can contain extraneous material alongside the therapeutic DNA.

"It confounds this question of toxicity and toxic side effects of AAV perhaps because, again, going back, we don't have reference standards for the field," said Charles Venditti, a senior investigator with the National Human Genome Research Institute.

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At FDA meeting, gene therapy experts wrestle with field's blindspots - BioPharma Dive

Joe Rogan, who hosts one of the most popular podcasts on Spotify, wrongly claimed that the Pfizer and Moderna COVID-19 vaccines are "really gene therapy," conflating the vaccines pioneering mRNA technology with the experimental technique that involves modifying genes to treat or cure disease.

The inaccurate claim came about 51 minutes into the Aug. 20 episode of "The Joe Rogan Experience" as Rogan discussed the vaccines with guest Meghan Murphy, a Canadian freelance writer and journalist.

Heres what Rogan said:

"It's not really a vaccine in the traditional sense. A vaccine is where they take a dead virus, and they turn it into a vaccine, and they inject it into your body so that your body fights off it develops the antibodies, and your body understands what that is, whether it's the measles or polio, it knows how to fight it off.

"This is really gene therapy. It's a different thing. Its tricking your body into producing spike protein and making these antibodies for COVID. But its only good for a few months, theyre finding out now. The efficacy wanes after five or six months. Im not saying that people shouldnt take it. But Im saying, youre calling it a thing that its not. Its not exactly what youre saying it is, and youre mandating people take it."

Theres no national mandate requiring that all Americans get vaccinated against COVID-19, although many employers and university systems are requiring it. And Rogan based his claim about the COVID-19 vaccines partly on an outdated conception of what a vaccine is.

But the bigger problem with the claim is that it mischaracterizes the technology used by the Pfizer and Moderna vaccines. The technology does not amount to gene therapy, public health experts said.

"It's absolutely incorrect to say that vaccines are really gene therapy," said Cindy Prins, clinical associate professor of epidemiology at the University of Florida. "Vaccines don't make any changes to your own DNA, so they don't edit your own DNA like gene therapy does. They also don't replace any mutated genes in your body."

No genetic material enters the part of the cell that hosts DNA as a result of the mRNA vaccines.

Rogan and Spotify did not offer on-the-record comments for this fact-check.

How the mRNA COVID-19 vaccines work

The Centers for Disease Control and Prevention defines a vaccine as "a product that stimulates a persons immune system to produce immunity to a specific disease."

"Basically, a vaccine is a way to get your immune system to recognize something and create antibodies to it," said Richard Watanabe, professor of population and public health sciences at the University of Southern California.

The Pfizer and Moderna vaccines fit that definition, the CDC says. While they work differently than many other familiar vaccines relying on messenger RNA, or mRNA, technology they still trigger an immune response inside the body, offering vital protection.

Older methods of vaccination included inoculating people with inactivated versions of viruses, and some vaccines for other diseases still work that way. But that method has proven at times to be risky, Watanabe said, citing the infamous "Cutter Incident" of 1955, in which some polio vaccines were not properly inactivated and tens of thousands of people were accidentally injected with the live virus.

The mRNA technology in the Pfizer and Moderna COVID-19 vaccines is newer, though research on it dates back to the 1990s.

The vaccines work by instructing the cells to make versions of a harmless spike protein found on the surface of the coronavirus, so the immune system can recognize the protein and mount an antibody response against the virus in the event of a future infection, the CDC says.

The third COVID-19 vaccine available in the U.S., from Johnson & Johnson, delivers similar instructions using an adenovirus thats been altered to make it harmless.

"Its true that mRNA vaccines are a major departure from traditional vaccines," said Dr. Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security. "They contain just the genetic material of the gene of interest in the pathogen that codes for the protein needed for immunity. Thats what makes them so path-breaking."

The mRNA vaccine technology isnt really gene therapy

While both mRNA vaccination and gene therapy involve genetic technology, they are different things, experts said.

Gene therapy involves modifying a persons genes to cure or treat a disease, according to the Food and Drug Administration. The FDA says it can work by replacing a disease-causing gene in the body with a healthy version, turning off the disease-causing gene, or introducing a new gene entirely. Only a few gene therapies have been fully approved, said Prins.

"Gene therapy is used to replace or fix genetic mutations that lead to diseases like cystic fibrosis, neuromuscular disease, inherited blindness and other genetic conditions," Prins said. "Gene therapy is not used in vaccines at all, since vaccines don't replace or edit your own genes."

Gene therapy corrects a genetic defect by delivering the gene, or DNA, to the nucleus, the part of the cell where DNA is located, Adalja said.

The mRNACOVID-19 vaccines are designed around the genetic structure of the virus. They carry mRNA, which teaches the immune system to identify the coronavirus, but they do not alter the recipients genetic makeup or DNA. The mRNA strands never enter the nucleus of the cell after vaccination.

To cross into the nucleus, the mRNA chains from the shots would need a special enzyme, according to WebMD. And they would need another enzyme to be integrated into the DNA. They dont have those enzymes.

"Its really just a different approach to delivering what the immune system needs to see in order to create the antibodies," Watanabe said of the mRNA vaccines.

The mRNA strands also break down shortly after entering the body, unlike with gene therapy, Prins said.

"It sticks around in the cell only long enough to be used as a recipe to make some spike protein that the immune system can then detect and respond to," Prins said. "After a few days, your cells will break up that mRNA into small pieces. So the recipe gets torn up. The spike protein that was made will stay around a little longer, up to a few weeks, which helps you build that immune response. But it will also get broken down so it doesn't stay for long."

Moderna says on its website that while mRNA and gene therapy might sound similar, they "take fundamentally different approaches." The company wrote:

"Gene therapy and gene editing alter the original genetic information each cell carries. The goal is to produce a permanent fix to the underlying genetic problem by changing the defective gene ... Unlike gene editing and gene therapy, mRNA technology does not change the genetic information of the cell, and is intended to be short-acting."

In the same podcast episode, Rogan claimed that "its not supported by science" for people who have previously been sick with COVID-19 to get the shots. But public health experts recommend that people who have had COVID-19 already get immunized anyway, because the science shows they provide better and broader protection than natural immunity.

Our ruling

Rogan said the mRNA COVID-19 vaccines are "really gene therapy."

Thats wrong. The two interventions are not the same. Gene therapy involves modifying genes to cure or treat a disease.

The COVID-19 vaccines from Pfizer and Moderna use mRNA technology to instruct the cells to recognize a spike protein on the coronavirus and mount a response against it, but they make no changes to the recipients genetic makeup or DNA. The mRNA strands never enter the part of the cell that hosts DNA, and they are broken down soon after they are introduced into the body.

We rate Rogans claim False.

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Continued here:

Joe Rogan falsely says mRNA vaccines are 'gene therapy' - PolitiFact

Dive Brief:

Most gene therapies currently in development use small viruses called AAVs, or adeno-associated viruses, to shuttle helpful genetic material into human cells.

When given intravenously, as is usually the case, these AAV-based therapies travel straight to the liver, where they're then processed. The liver therefore acts as a window into how patients respond to treatment with gene therapy, and provides alerts when problems may arise.

Indeed, liver toxicity, often diagnosed by elevated enzyme levels but sometimes by damage to the organ,is the most common adverse event in clinical trials testing intravenously administered AAV vectors. And though toxicity can be managed, some cases are serious enough that they require longer care or even hospitalization.

In one example cited by the FDA, certain patients treated with Zolgensma, the Novartis gene therapy for spinal muscular atrophy, needed corticosteroids for more than seven months to deal with liver toxicity issues. According to the agency, among the roughly 800 patients who've received Zolgensma thus far, about a third have experienced at least one instance of liver toxicity.

Liver toxicity has also come into focus for AAV gene therapies targeting hemophilia, as well as for the one Astellas is developing. The safety concerns are significant enough that, later this week, the FDA is convening a group of gene therapy experts to assess the risks involved when using AAV vectors for gene therapy.

For Astellas, a voluntary pause on screening and dosing is another hard-felt setback.

So far, the AT132 trial has administered the therapy to 24 patients, with seven on the lower dose and 17 on the higher. Three participants on the higher dose developed a progressive form of hepatitis that led to liver failure. Those patients later died from either sepsis or gastrointestinal bleeding as a result of the liver failure.

One patient on the lower dose has now experienced liver problems too. Astellas said in a statement Wednesday that the patient, like some others with X-linked myotubularmyopathy, has a history of intermittent cholestasis, a condition which disrupts the flow of bile from the liver.

The company noted, though, that before receiving AT132, the patient had a "normal" liver ultrasound and liver function test results which met the trial's eligibility criteria.

Astellas said it will be closely monitoring the patient and, if the FDA ultimately issues a clinical hold, it will "review the content and determine next steps."

"As we learn more about the case, we will incorporate any new observations into our ongoing investigation in order to have a well-informed discussion with the independent Data Monitoring Committee, our Liver Advisory Panel, and study investigators," said Nathan Bachtell, head of gene therapy, medical and development at Astellas.

"Given previous hepatic events within the program, any one [serious adverse event] needs to be viewed both individually and in the context of the broader program as we move forward," Bachtell added.

Astellas acquired AT132 through its $3 billion acquisition of Audentes Therapeutics, which has since been rebranded as an independent subsidiary named "AstellasGene Therapies." Amid this transition, the former chief executive at Audentes,Natalie Holles,left the combined company in April for undisclosed reasons.

Astellas is also working on other gene therapies for Pompe disease, Duchenne muscular dystrophy and myotonic dystrophy type 1.

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Astellas again hits pause on gene therapy trial - BioPharma Dive

SAN FRANCISCO, Sept. 1, 2021 /PRNewswire/ --The global cell and gene therapy manufacturing marketsize is expected to reach USD 57.4 billion by 2028, according to a new report by Grand View Research, Inc. The market is estimated to expand at a CAGR of 20.3% from 2021 to 2028. An exponential rise in clinical pipeline coupled with a rising number of regulatory approvals for advanced therapies has majorly driven the market.

Key Insights & Findings:

Read 188 page market research report, "Cell And Gene Therapy Manufacturing Market Size, Share & Trends Analysis Report By Therapy Type, By Scale (R&D, Commercial), By Mode, By Workflow (Vector Production, Cell Banking), By Region, And Segment Forecasts, 2021 - 2028", by Grand View Research

Considering promising growth opportunities in the contract development of cellular and gene-modified therapies, market participants are making focused efforts to boost their market presence. Also, bio manufacturers are signing strategic alliances with contract manufacturers to accelerate the R&D of their candidate programs. Rising demand for CMOs/CDMOs services has led to the entry of several new players as well as expansion of product development capabilities, thereby positively impacting market revenue.

Several novel methods are being introduced to advance cell and gene therapy manufacturing. For instance, the manufacturers are exploring the potential of single-use technology in production workflows. This technique is gaining increasing attention in this arena to speed the development process while reducing the overall cost and production timeline. Such technological advancements in space are anticipated to bolster market growth in the coming years.

Grand View Research has segmented the global cell and gene therapy manufacturing market on the basis of therapy type, scale, mode, workflow, and region:

List of Key Players of Cell And Gene Therapy Manufacturing Market

Check out more studies related to genetics and cell therapy, conducted by Grand View Research:

Browse through Grand View Research's coverage of the Global Biotechnology Industry.

Gain access to Grand View Compass, our BI enabled intuitive market research database of 10,000+ reports

About Grand View Research

Grand View Research, U.S.-based market research and consulting company, provides syndicated as well as customized research reports and consulting services. Registered in California and headquartered in San Francisco, the company comprises over 425 analysts and consultants, adding more than 1200 market research reports to its vast database each year. These reports offer in-depth analysis on 46 industries across 25 major countries worldwide. With the help of an interactive market intelligence platform, Grand View Research helps Fortune 500 companies and renowned academic institutes understand the global and regional business environment and gauge the opportunities that lie ahead.

Contact:

Sherry JamesCorporate Sales Specialist, USAGrand View Research, Inc.Phone: 1-415-349-0058Toll Free: 1-888-202-9519Email: [emailprotected]Web: https://www.grandviewresearch.comFollow Us: LinkedIn| Twitter

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Cell And Gene Therapy Manufacturing Market Size Worth $57.4 Billion By 2028: Grand View Research, Inc. - PRNewswire

Posted: Sep 3, 2021 / 11:14 AM EDT / Updated: Sep 3, 2021 / 11:14 AM EDT

HARTFORD, Conn., (WTNH) Connecticut Childrens announced that it is now the first hospital in the state to be in contract with Cignas Gene Therapy Program on Friday.

The Cigna Gene Therapy Program will give covered families have immediate access to the therapy, and have affordable options for previously expensive gene therapy medication.

Families covered by Cigna can more want gene therapy for children with spinal muscular atrophy while avoiding $2 million worth of medicine. According to Cignas website, the provided medicine will be available to covered families for less than $1 a month.

Connecticut Childrens is committed to finding innovative treatments for devastating diseases, but at a price that wont bankrupt families, said Jim Shmerling, DHA, FACHE, President & CEO of Connecticut Childrens. We have an obligation to all children to ensure they can access to the specialists and cutting edge treatments they need at all times.

Expensive therapies for rare diseases are posing a challenge for healthcare. As shown in reports, many families have to make difficult decisions in order to pay for the necessary medicine. EvaluatePharma research shows that by 2024, the cost of gene therapy in the U.S. will be over $16 billion.

As drug prices continue to climb, we have an obligation to work for our patients and families and continue advocating on their behalf to the insurance companies and lawmakers, said Shmerling. All children deserve access to these kinds of therapies.

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Connecticuts Children first to enroll affordable gene therapy - WTNH.com

Global Gene Therapy Market

Gene therapy is a type of experimental technique in which genes are used to treat or prevent diseases. In this therapy genes are inserted into patients cells instead of using surgery and drugs. Gene therapy has various approaches such as replacement of muted gene, inactivating or knocking out a muted gene, and introducing new gene into the body to help fight a disease.

Get Sample Copy of this Report @https://qualiketresearch.com/request-sample/Gene-Therapy-Market/request-sample

Increase in prevalence of chronic diseases like cancer is expected to boost the global gene therapy market, in this forecast period. Furthermore, rise in technological advancements in genomics and gene-editing tool will have the positive impact on gene therapy market growth. In other hand, rapid and significant progress in the molecular and cellular biology arena is expected to propel the global gene therapy market growth. Moreover, rise in product approval is expected to fuel the global gene therapy market growth.

The better understanding of the market demands a better handling of macroeconomic and microeconomic aspects that are projected to mark the progress. These factors, if guided well, can helm the target market to prosperity by wading via rough waters, all the while, keeping plummeting curves at bay. With real-time data, the Global Gene Therapy Market report is projected to provide a detailed picture of the demographic possibilities, which would assist key players in assessing growth opportunities & significantly establishing parameters which would continue to influence the market in the upcoming years.

However, high cost is the major restraining factor which is expected to hamper the global gene therapy market growth. Also, lack of skilled professionals is expected to affect the global gene therapy market growth.

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Global Gene Therapy Market Segmentation

Global Gene Therapy Market is segmented into vector type such as Viral Sector, and Nonviral Sector, by gene type such as Antigen, Cytokine, Growth Factors, Receptors, and Others. Further, Global Gene Therapy Market is segmented into application such as Oncological Disorder, Cardiovascular Diseases, Neurological Disorders, Rare Diseases, Infectious Diseases, and Others.

Also, Global Gene Therapy Market is segmented into five regions such as North America, Latin America,Europe, Asia Pacific, and Middle East and Africa.

Global Gene Therapy Market Key Players

Various key players are discussed in this report such as BIGEN, Gilead Sciences Inc., Amgen, Novartis AG, Bluebird Bio, Inc, Orchard Therapeutics Plc, Spark Therapeutics ,Human Stem cell Institutes, JAZZ Pharmaceuticals, Sibiono Genetech Co,ltd, UNIQURE N.V,Mustang Bio, and Poseida Therapeutics Inc.

The regional distribution of the Global Gene Therapy Market is also covered in the report, and detailed analysis are provided for the markets segment in each major region. The regional markets are discussed to give players clear idea of where each region is soaring & what needs attention in specific markets. Region-specific strategies as well as product formulations can be based on this detailed analysis, as the factors making the market tick in particular regions are analysed in the report, leading to a comprehensive understanding of the Global Gene Therapy Market.

Browse Full Research Report @https://qualiketresearch.com/reports-details/Gene-Therapy-Market

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QualiKet Research is a leading Market Research and Competitive Intelligence partner helping leaders across the world to develop robust strategy and stay ahead for evolution by providing actionable insights about ever changing market scenario, competition and customers. QualiKet Research is dedicated to enhancing the ability of faster decision making by providing timely and scalable intelligence. We use different intelligence tools to come up with evidence that showcases the threats and opportunities which helps our clients outperform their competition.

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Global Gene Therapy Market Top Companies, Size, Growth Analysis, Segmentation, Industry Outlook Analysis , and Forecast 2020 to 2027 UNLV The Rebel...

2021 is on track to have the highest number of regulatory approvals of gene therapy and gene-modified cell therapy products. Credit: Shutterstock

To access the report and other gold-standard data, get in touch with GlobalData today.

In August 2021, the Alliance for Regenerative Medicine (ARM), in collaboration with GlobalData, published a new report highlighting that 2021 has already been a year of firsts and records for the regenerative medicine sector with significant clinical milestones, commercial progress and investment.

For example, CRISPR gene-editing technology was used for the first time in vivo, with Intellia Therapeutics announcing promising Phase I data from a clinical trial of NTLA-2001 in transthyretin (ATTR) amyloidosis patients. Using data from GlobalDatas Clinical Trial Intelligence database, the report also shows that there are over 2,600 trials for regenerative medicines ongoing worldwide, including over 1,300 industry-sponsored trials and with almost 250 in Phase III. In terms of investment, the sector raised a record $14bn in H1 2021, compared to $19.9bn for all of 2020.

In addition, 2021 is on track to have the highest number of regulatory approvals of gene therapy and gene-modified cell therapy products, with three approvals to date and four expected to get the green light by the end of the year. The report also highlights that Europe could be at risk of falling behind the US and Asia in terms of number of developers and new clinical trials.

Initiatives by ARM to educate policymakers and payers in the US and Europe on regenerative medicines are also addressed in the report. For example, ARM has assisted in shaping US policy by working with congressional sponsors on Cures 2.0 legislation and advocating for increased funding for the FDAs Center for Biologics Evaluation and Research (CBER). In Europe, ARM was involved in removing a reimbursement hurdle for hospitals in Germany that provide regenerative medicines.

To access the report and other gold-standard data, get in touch with GlobalData today.

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Regenerative medicine 2021: report highlights record year for the sector - Clinical Trials Arena

Season 1 of Science Will Win is a four-part miniseries exploring the science behind gene therapy; the next generation of medicines which could bring new possibilities for patients living with rare genetic diseases.

Listeners will hear from a diverse line-up of leading experts on the future-shaping science, challenging policy environment and the personal stories which remain our guiding-light in the search for breakthrough therapies of tomorrow.

At a time when innovative science is achieving the seemingly impossible, well look at gene therapy from every angle, speaking to the Pfizer scientists and experts on the forefront of medical research, as well as the patients and families who are holding new hope in the life-changing potential of gene therapy.

Subscribe and follow Science Will Win to make sure you dont miss an episode.

Season 1 of Science Will Win is hosted by Adam Rutherford, a geneticist, writer, broadcaster and Honorary Fellow at University College London (UCL), U.K. After studying evolutionary biology at UCL, Adam gained a PhD from Great Ormond St Hospital and the Institute of Child Health, London, in the genetics of the developing eye and was also part of the team that identified the first genetic cause of a form of childhood blindness. Since then, Adam spent ten years as an editor for the science journal, Nature, as well as writing and featuring in an array of BBC television, radio and podcast programmes.

Science Will Win is a podcast that takes listeners under the microscope of some the most promising medical innovations, exploring therapies which have the potential to shape the future of healthcare and offer new hope to patients around the world.

Through conversations with a diverse line-up of guests, including scientists and experts, patient advocates and, most importantly, patients themselves, each miniseries focuses on a unique healthcare challenge, diving into the fascinating science, policy challenges and potential to transform patients lives for the better.

This podcast is powered by Pfizer. The information, statements, comments, views and opinions expressed by those guests featured in this podcast are their own and not necessarily representative of the views and opinions of Pfizer Inc.

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Science Will Win Podcast: Season 1 - Pfizer

PARIS--(BUSINESS WIRE)--Regulatory News:

GenSight Biologics (Paris:SIGHT)(Euronext: SIGHT, ISIN: FR0013183985, PEA-PME eligible), a biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders, today announced that the Journal of Neuro-Ophthalmology (JNO) has published results from RESTORE, the long-term follow-up study of LUMEVOQ, which show sustained treatment effect from a unilateral injection of LUMEVOQ three years after injection in the RESCUE and REVERSE trials.

The paper*, published in the September issue of JNO under the title Long-Term Follow-Up After Unilateral Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy: The RESTORE Study, presents analyses that show sustained improvement in best-corrected visual acuity (BCVA) and quality of life scores three years after subjects received LUMEVOQ treatment. The continuous improvement in BCVA was demonstrated in both eyes of the unilaterally treated patients, confirming the contralateral treatment effect reported in the RESCUE and REVERSE trials.

It is gratifying to see this sustained outcome, commented lead author Dr. Valrie Biousse, MD, Departments of Ophthalmology and Neurology, Emory University School of Medicine, Atlanta, GA. Dr. Biousse, who was also an coinvestigator in the RESCUE and REVERSE trials, added, This is further evidence of a bilateral therapeutic effect of a single unilateral gene therapy injection.

Mean BCVA steadily improved to 1.26 LogMAR at 48 months after onset (3 year-post injection), remaining onchart (i.e., better than 1.6 LogMAR) throughout the follow-up period. A locally-estimated scatterplot smoothing (LOESS) regression analysis illustrates the progressive and sustained improvement of BCVA in RESTORE subjects (Figure 1) since treatment with LUMEVOQ.

In addition, subjects quality of life continued to improve between Year 2 and Year 3 post-injection, as documented by scores reported in the visual function questionnaire VFQ-25. Relative to baseline, the mean VFQ-25 composite score (averaging 11 visionrelated subscales) was higher by 4 points at Year 2 and 7 points at Year 3. At Year 3, clinically meaningful improvement from baseline were seen in the sub-scores that corresponded to mental health (+21 points), role difficulties (+17 points), dependency (+15 points), general vision (+9 points), near activities (+6 points), and distance activities (+5 points).

RESCUE and REVERSE were randomized, double-masked, sham-controlled, Phase III clinical trials that assessed the efficacy and safety of LUMEVOQ gene therapy as a treatment for vision loss due to ND4-LHON. The only difference between the two studies was the duration of vision loss at screening: RESCUE subjects had vision loss for less than 6 months, while REVERSE subjects had vision loss for 6 to 12 months. The 72 subjects who completed the Phase III trials RESCUE and REVERSE were invited to participate in RESTORE, and 62 (86.1%) agreed to be monitored up to five years after treatment.

The paper is available at: https://journals.lww.com/jneuro-ophthalmology/Fulltext/2021/09000/Long_Term_Follow_Up_After_Unilateral_Intravitreal.5.aspx.

*About the paper:

Long-Term Follow-Up After Unilateral Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy: The RESTORE Study

Authors: Valrie Biousse, MD1, Nancy J. Newman, MD1, Patrick Yu-Wai-Man, MD, PhD2,3,4,5, Valerio Carelli, MD PhD6,7 , Mark L. Moster, MD8, Catherine Vignal-Clermont, MD9,10, Thomas Klopstock, MD11,12,13, Alfredo A. Sadun, MD, PhD14, Robert C. Sergott, MD8, Rabih Hage, MD10, Simona Esposti, MD4, Chiara La Morgia, MD, PhD6,7, Claudia Priglinger, MD15, Rustum Karanja, MD, PhD14,16, Laure Blouin, MSc17, Magali Taiel, MD17, Jos-Alain Sahel, MD, PhD10,18,19,20 for the LHON Study Group

Affiliations:

About GenSight Biologics

GenSight Biologics S.A. is a clinical-stage biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders. GenSight Biologics pipeline leverages two core technology platforms, the Mitochondrial Targeting Sequence (MTS) and optogenetics, to help preserve or restore vision in patients suffering from blinding retinal diseases. GenSight Biologics lead product candidate, LUMEVOQ (GS010; lenadogene nolparvovec), has been submitted for marketing approval in Europe for the treatment of Leber Hereditary Optic Neuropathy (LHON), a rare mitochondrial disease affecting primarily teens and young adults that leads to irreversible blindness. Using its gene therapy-based approach, GenSight Biologics product candidates are designed to be administered in a single treatment to each eye by intravitreal injection to offer patients a sustainable functional visual recovery.

About Leber Hereditary Optic Neuropathy (LHON)

Leber Hereditary Optic Neuropathy (LHON) is a rare maternally inherited mitochondrial genetic disease, characterized by the degeneration of retinal ganglion cells that results in brutal and irreversible vision loss that can lead to legal blindness, and mainly affects adolescents and young adults. LHON is associated with painless, sudden loss of central vision in the 1st eye, with the 2nd eye sequentially impaired. It is a symmetric disease with poor functional visual recovery. 97% of patients have bilateral involvement at less than one year of onset of vision loss, and in 25% of cases, vision loss occurs in both eyes simultaneously. The estimated incidence of LHON is approximately 800-1,200 new patients who lose their sight every year in the United States and the European Union.

About LUMEVOQ (GS010; lenadogene nolparvovec)

LUMEVOQ (GS010; lenadogene nolparvovec) targets Leber Hereditary Optic Neuropathy (LHON) by leveraging a mitochondrial targeting sequence (MTS) proprietary technology platform, arising from research conducted at the Institut de la Vision in Paris, which, when associated with the gene of interest, allows the platform to specifically address defects inside the mitochondria using an AAV vector (Adeno-Associated Virus). The gene of interest is transferred into the cell to be expressed and produces the functional protein, which will then be shuttled to the mitochondria through specific nucleotidic sequences in order to restore the missing or deficient mitochondrial function. LUMEVOQ was accepted as the invented name for GS010 (lenadogene nolparvovec) by the European Medicines Agency (EMA) in October 2018.

About RESCUE, REVERSE, and RESTORE

RESCUE and REVERSE were two separate randomized, double-masked, sham-controlled Phase III trials designed to evaluate the efficacy of a single intravitreal injection of GS010 (rAAV2/2-ND4) in subjects affected by LHON due to the G11778A mutation in the mitochondrial ND4 gene.

The primary endpoint measured the difference in efficacy of GS010 in treated eyes compared to sham-treated eyes based on BestCorrected Visual Acuity (BCVA), as measured with the ETDRS at 48 weeks post-injection. The patients LogMAR (Logarithm of the Minimal Angle of Resolution) scores, which are derived from the number of letters patients read on the ETDRS chart, were used for statistical purposes. Both trials were adequately powered to evaluate a clinically relevant difference of at least 15 ETDRS letters between drug-treated and sham-treated eyes, adjusted to baseline.

The secondary endpoints involved the application of the primary analysis to bestseeing eyes that received GS010 compared to those receiving sham, and to worseseeing eyes that received GS010 compared to those that received sham. Additionally, a categorical evaluation with a responder analysis was performed, including the proportion of patients who maintained vision (< ETDRS 15L loss), the proportion of patients who gained 15 ETDRS letters from baseline and the proportion of patients with Snellen acuity of >20/200. Complementary vision metrics included automated visual fields, optical coherence tomography, and color and contrast sensitivity, in addition to quality-of-life scales, biodissemination and the time course of immune response. Readouts for these endpoints were at 48, 72 and 96 weeks after injection.

The trials were conducted in parallel, in 37 subjects for REVERSE and 39 subjects for RESCUE, in 7 centers across the United States, the UK, France, Germany and Italy. Week 96 results were reported in 2019 for both trials, after which patients were invited to participate in a long-term follow-up study, RESTORE, for three additional years.

The primary objective is to assess the long-term safety of intravitreal LUMEVOQ administration up to 5 years post-treatment. The secondary objective is to assess the long-term treatment efficacy of the therapy and the quality of life (QoL) in subjects up to 5 years post-treatment. The first subject was enrolled on January 9, 2018. 61 subjects have enrolled.

ClinicalTrials.gov Identifiers:REVERSE: NCT02652780RESCUE: NCT02652767RESTORE: NCT03406104

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GenSight Biologics Announces Publication of RESTORE Study Data Demonstrating Sustained Efficacy 3 Years After Unilateral Injection of LUMEVOQ -...