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

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.

RELATED: Spotifys Joe Rogan repeats inaccurate claim that they are monitoring SMS texts

RELATED: Youth is not invincible: 9 experts dispute Joe Rogans vaccine advice for healthy 21-year-olds

Continued here:

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

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

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

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...

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

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

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 -...

Novartis and the Bill and Melinda Gates Foundation are joining forces to discover and develop a gene therapy to cure sickle cell disease with a one-step, one-time treatment that is affordable and simple enough to treat patients anywhere in the world, especially in sub-Saharan Africa where resources may be scarce but disease prevalence is high.

The three-year collaboration, announced Wednesday, has initial funding of $7.28 million.

Current gene therapy approaches being developed for sickle cell disease are complex, enormously expensive, and bespoke, crafting treatments for individual patients one at a time. The collaboration aims to instead create an off-the-shelf treatment that bypasses many of the steps of current approaches, in which cells are removed and processed outside the body before being returned to patients.

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Sickle cells cause is understood. The people it affects are known. But its cure has been elusive, Jay Bradner, president of the Novartis Institutes for BioMedical Research, told STAT.

We understand perfectly the disease pathway and the patient, but we dont know what it would take to have a single-administration, in vivo gene therapy for sickle cell disease that you could deploy in a low-resource setting with the requisite safety and data to support its use, he said. Im a hematologist and can assure you that in my experience in the clinic, it was extremely frustrating to understand a disease so perfectly but have so little to offer.

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Sickle cell disease is a life-threatening inherited blood disorder that affects millions around the world, with about 80% of affected people in sub-Saharan Africa and more than 100,000 in the U.S. The mutation that causes the disease emerged in Africa, where it protects against malaria. While most patients with sickle cell share African ancestry, those with ancestry from South America, Central America, and India, as well as Italy and Turkey, can also have the hereditary disease.

The genetic mutation does its damage by changing the structure of hemoglobin, hampering the ability of red blood cells to carry oxygen and damaging blood vessels when the misshapen cells get stuck and block blood flow. Patients frequently suffer painful crises that can be fatal if not promptly treated with fluids, medication, and oxygen. Longer term, organs starved of oxygen eventually give out. In the U.S., that pain and suffering is amplified when systemic and individual instances of racism deny Black people the care they need.

Delivering gene therapy for other diseases has been costly and difficult even in the best financed, most sophisticated medical settings. Challenges include removing patients cells so they can be altered in a lab, manufacturing the new cells in high volume, reinfusing them, and managing sometimes severe responses to the corrected cells. Patients also are given chemotherapy to clear space in their bone marrow for the new cells.

Ideally, many of those steps could be skipped if there were an off-the-shelf gene therapy. That means, among other challenges, inventing a way to eliminate the step where each patients cells are manipulated outside the body and given back the in vivo part of the plan to correct the genetic mutation.

Thats not the only obstacle. For a sickle cell therapy to be successful, Bradner said, it must be delivered only to its targets, which are blood stem cells. The genetic material carrying corrected DNA must be safely transferred so it does not become randomly inserted into the genome and create the risk of cancer, a possibility that halted a Bluebird Bio clinical trial on Tuesday. The payload itself mustnt cause such problems as the cytokine storm of immune overreaction. And the intended response has to be both durable and corrective.

In a way, the gene delivery is the easy part because we know that expressing a normal hemoglobin, correcting the mutated hemoglobin, or reengineering the switches that once turned off normal fetal hemoglobin to turn it back on, all can work, Bradner said. The payload is less a concern to me than the safe, specific, and durable delivery of that payload.

For each of these four challenges delivery, gene transfer, tolerability, durability there could be a bespoke technical solution, Bradner said. The goal is to create an ensemble form of gene therapy.

Novartis has an existing sickle-cell project using CRISPR with the genome-editing company Intellia, now in early human trials, whose lessons may inform this new project. CRISPR may not be the method used; all choices are still on the table, Bradner said.

Vertex Pharmaceuticals has seen encouraging early signs with its candidate therapy developed with CRISPR Therapeutics. Other companies, including Beam Therapeutics, have also embarked on gene therapy development.

The Novartis-Gates collaboration is different in its ambition to create a cure that does not rely on an expensive, complicated framework. Novartis has worked with the Gates Foundation on making malaria treatment accessible in Africa. And in October 2019, the Gates Foundation and the National Institutes of Health said together they would invest at least $200 million over the next four years to develop gene-based cures for sickle cell disease and HIV that would be affordable and available in the resource-poor countries hit hardest by the two diseases, particularly in Africa.

Gene therapies might help end the threat of diseases like sickle cell, but only if we can make them far more affordable and practical for low-resource settings, Trevor Mundel, president of global health at the Gates Foundation, said in a statement about the Novartis collaboration. Its about treating the needs of people in lower-income countries as a driver of scientific and medical progress, not an afterthought.

Asked which is the harder problem to solve: one-time, in vivo gene therapy, or making it accessible around the world, David Williams, chief of hematology/oncology at Boston Childrens Hospital, said: Both are going to be difficult to solve. The first will likely occur before the therapy is practically accessible to the large number of patients suffering the disease around the world.

Williams is also working with the Gates Foundation, as well as the Koch Institute for Integrative Cancer Research at MIT, Dana-Farber Cancer Institute, and Massachusetts General Hospital, on another approach in which a single injection of a reagent changes the DNA of blood stem cells. But there are obstacles to overcome there, too, that may be solved by advances in both the technology to modify genes and the biological understanding of blood cells.

Bradner expects further funding to come to reach patients around the world, once the science progresses more.

There is no plug-and-play solution for this project in the way that mRNA vaccines were perfectly set up for SARS-CoV-2. We have no such technology to immediately redeploy here, he said. Were going to have to reimagine what it means to be a gene therapy for this project.

Read more:

Novartis, Gates Foundation pursue a simpler gene therapy for sickle cell - STAT

-- Gene editing expert Charles Albright, Ph.D., joins as chief scientific officer --

-- Gene therapy development expert Petra Kaufmann, M.D.,joins as chief medical officer

WALTHAM, Mass., Feb. 17, 2021 (GLOBE NEWSWIRE) -- Affinia Therapeutics, an innovative gene therapy company with a proprietary platform for rationally designed adeno-associated virus (AAV) vectors and gene therapies for rare and non-rare diseases, today announced the completion of its leadership team. Collectively, the executives represent a diverse team of proven leaders in gene therapy who have successfully developed novel platforms and translated them to medicines that have made a transformative difference in the lives of those affected by devastating diseases.

Our calling is to broaden the reach of gene therapies for patients in need, and this starts with our proven leadership team. Members of our team have been at the forefront of the field and come from a variety of eminent organizations to innovate in the gene therapy science and programs at Affinia Therapeutics, said Rick Modi, chief executive officer at Affinia Therapeutics. We believe in a vastly different future medical era of one-time potentially curative medicines for patients affected by diseases, rare and non-rare. But realizing this vision requires moving beyond conventional AAV serotypes. At Affinia Therapeutics, we are uniquely positioned to engineer novel vectors and gene therapies that direct tissue tropism and have the potential to improve clinical efficacy, as well as immunogenicity and safety. Together, Dr. Albright, Dr. Kaufmann and the rest of our leadership team will leverage their extensive experience to advance our platform and programs.

Dr. Albright joins Affinia Therapeutics from Editas Medicine, where he served as executive vice president and chief scientific officer and led the development of the CRISPR gene editing technology platform. In this role, he industrialized and matured the platform and translated it to pioneering programs through Investigational New Drug (IND) submissions that led to clinical trials. Prior to joining Editas, Dr. Albright spent over 12 years at Bristol Myers Squibb, where he most recently held the position of vice president, genetically defined diseases and genomics. As a research leader at both biotech and large pharmaceutical companies, he has honed his expertise across a range of therapeutic areas including neurology, neuromuscular, cardiovascular, ophthalmology and oncology. Dr. Albright earned a Ph.D. in biology at MIT and was a postdoctoral fellow at the Whitehead Institute.

Dr. Kaufmann is an expert in translational medicine and clinical development focused on neuroscience, rare disease and gene therapy. She recently served as senior vice president and head of clinical development, analytics and translational medicine at Novartis Gene Therapies. She directed clinical development activities that included the global development of Zolgensma and translational strategy for several pipeline programs. This followed many years of clinical research and development positions in academia and at the National Institutes of Health (NIH), where she held leadership roles of increasing responsibility, most recently as director of the Office of Rare Diseases Research. Dr. Kaufmann earned an M.D. at the University of Bonn and an M.S. in biostatistics at Columbia University, where she also trained in neurology and served as a tenured faculty member, advancing research and caring for patients.

It is exciting to see the platform generate advances beyond the conventional AAV serotypes discovered many years ago, said Dr. Albright. Affinia Therapeutics platform for engineering next-generation vectors with specific pharmacodynamic properties enables us to explore the potentially curative benefits of gene therapy in new indications. I look forward to leading the scientific team as we advance these insights into translational opportunities in the clinic and, ultimately, into transformative therapies for patients.

I am thrilled to join this team of gene therapy experts who are helping to broaden the reach of gene therapies, said Dr. Kaufmann. I look forward to putting my clinical research and development experience into practice as we translate our differentiated AAV vectors into transformative medicines for people suffering from diseases that have been inadequately addressed by conventional AAVs and traditional therapies.

Dr. Albright and Dr. Kaufmann join the following individuals on Affinia Therapeutics leadership and scientific advisory team:

This team has collectively authored more than 450 publications, holds more than 15 patents, held meaningful roles on more than 15 BLAs, supplemental BLAs and product launches, and has executed on more than $16 billion in value for IPOs and M&As.

About Affinia TherapeuticsAt Affinia Therapeutics, our purpose is to develop gene therapies that can have a transformative impact on people affected by devastating rare and non-rare diseases. Our proprietary platform enables us to methodically engineer novel AAV vectors and gene therapies with potentially improved tissue tropism, cell specificity, immunogenicity and safety. With our innovative science, we are working to broaden the reach of life-changing gene therapies to meaningful numbers of patients with an initial focus on central nervous system (CNS) and muscle diseases with significant unmet need. http://www.affiniatx.com.

Affinia Therapeutics Contacts

Investors: investors@affiniatx.com

Media: media@affiniatx.com

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Affinia Therapeutics Announces Addition of Gene Therapy Scientific and Medical Experts to Leadership Team to Advance Novel Gene Therapy Platform and...

HOUSTON, Feb. 16, 2021 /PRNewswire/ -- Avance Biosciences Inc., a leading CRO providing GLP/GMP-compliant assay development, assay validation, and sample testing services supporting biological drug development and manufacturing, announced today that its Houston facility, which successfully passed an inspection by the U.S. Food and Drug Administration in Oct 2018, is undergoing major expansion to handle rapidly growing demand for their services.

The new facility, expected to be completed by Q3 2021, is located adjacent to the current facility and will expand the Houston campus by an additional 5,500 square feet. The new facility will be devoted to cell-based assay services and enable Avance to better address the specific needs of their GMP clients. Additionally, Avance is expanding their mammalian cell culture related assay capabilities including: mycoplasma testing, adventitious agents testing, sterility, potency, and others.

As a provider of genomics and biological testing services, Avance Biosciences offers a broad range of molecular biology and microbiology assays in compliance with current Good Manufacturing Practices (21 CFR Parts 210 & 211) and Good Laboratory Practices (21 CFR Part 58) to support its clients' regulatory submissions.

Avance's CEO, Dr. Xuening Huang commented, "We take a partnership approach with our clients and that means an extended relationship; from discovery to development to clinical testing and on to manufacturing. Our most recent expansions will ensure that we can keep pace with our customer's increased needs when ramping up development and manufacturing activities. Our primary goals are to deliver world-class service and complete customer satisfaction."

Avance's Vice President of Sales and Marketing, Cal Froberg commented, "It's clear there is tremendous growth in the development of cell and gene therapies and we're proactively managing resources to handle increased market demand for related support services. The industry is expanding rapidly and Avance is positioned well to address the specific needs of these customers."

This most recent expansion comes on the heels of another 7,500 square foot expansion completed in 2020 which has significantly increased Avance's NGS and ddPCR capabilities. This facility has been pivotal in addressing gene therapy development support needs such as: edited gene testing, gene integration assays, and DNA/RNA biodistribution studies.

Recently, Avance Biosciences was recognized as a top 10 Genomics Solutions Company for 2020. Current and future expansion plans will serve to solidify this position among the premier providers in this space.

About Avance Biosciences

Avance offers cGMP/GLP compliant genomics biological testing services in support of drug development and manufacturing. Its leading scientists have designed, validated, and tested thousands of assays under cGMP/GLP regulations for the FDA, EPA, and European and Japanese regulatory agencies. Avance's team has extensive knowledge and experience working with scientists, QA/QC professionals and project managers from over 100 pharmaceutical and biotechnology companies and organizations throughout the world.

Contact

Xuening Huangxuening.huang@avancebio.com877-909-52109770 West Little York RoadHouston, TX 77040 USA

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SOURCE Avance Biosciences

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Avance Biosciences Expanding Houston Campus in Support of Cell and Gene Therapy Drug Development - BioSpace

New data from GenSight Biologics showed promising results for lenadogene nolparvovec (LUMVOQ), an intravitreal gene therapy for leber hereditary optic neuropathy (LHON) caused by mutations in the mitochondrial ND4 gene.

Overall, the therapy was well-tolerated in patients, had a favorable safety profile, and was shown that it may lead to clinically meaningful improvements.

A team, led by Catherine Vignal-Clermont, MD, Rothschild Foundation Hospital, Paris, France, conducted an open-label, single-center, dose-escalation study that primarily assessed safety and tolerability of the gene therapy among 15 patients with LHON.

Therapeutic options for adolescent and adult patients with LHON are currently limited to idebenone (Raxone), a synthetic analog of coenzyme Q10, which is approved only in Europe under exceptional circumstances for treatment of LHON, Vignal-Clermont and team wrote.

They further acknowledged that no approved treatment exists in the United States.

REVEAL A Phase I/IIa Study

Among the exclusion criteria were vision loss in the fellow eye, glaucoma, diabetic retinopathy, macula edema, vitreoretinal disease, pathology of the retina or the optic nerve, retinal vein occlusion, narrow angles, optic neuropathy for other causes, or any other disease that would have an effect on visual function.

Eligible patients were divided into a dosing cohort to receive a single injection and then were followed-up immediately at day 3 for safety and efficacy assessments.

The investigators pursued further follow-up at weeks 1, 2, 4, 8, 12, 24, 36, and 48 post-treatment. Additional follow-up was performed at years 1.5, 2, 2.5, 3, 4, and 5.

The studys primary endpoint was the overall incidences of adverse events up to 5 years post-treatments for each dosing level and for the treatment as a whole.

Secondary endpoints included best corrected visual acuity (BCVA; calculated as logarithm of the minimal angle of resolution [LogMAR]), among other efficacy measurements.

Results

Throughout the follow-up period, the investigators noted no serious adverse events that were considered related to treatments.

Furthermore, patients did not experience unexpected adverse events nor grades 3 or 4 Common Terminology Criteria for Adverse Events.

Anterior chamber inflammation and vitritis were mostly managed with topical steroids, and ocular inflammation was considered to be dose limiting by the independent data safety monitoring board based on the benefits/risks for the subjects, the investigators wrote.

In terms of efficacy, the team reported that analysis of the LogMAR BCVA in both treated and untreated eyes showed clinically relevant and durable improvements compared with baseline.

As such, the mean improvement for the treated eye was -0.44 LogMAR and for the untreated eye was -0.49.

Thus, at 5 years post-treatment, the final value of LogMAR was +1.96 and +1.85, respectively, for the treated and untreated eyes.

As for those treated with the optimal dose level of 9 1010 viral genomes/eye (n = 6), the mean visual acuity improvement from baseline was 0.68 LogMAR for treated eyes and 0.64 LogMAR for untreated eyes.

The final mean value for the treated and untreated eyes were LogMAR +1.77 and +1.78, respectively.

While there was a meaningful improvement in visual acuity for REVEAL subjects, the final visual acuity was less favorable than that seen in the two subsequent pivotal phase III studies in which subjects were treated earlier during the course of their disease, Vignal-Clermont and colleagues wrote.

Nevertheless, the team acknowledged that these findings are a promising prelude to the Phase III RESCUE and REVERSE studies, which are running in tandem and currently assessing the efficacy of the single injection of the gene therapy in a larger population.

The study, "Safety of Intravitreal Gene Therapy for Treatment of Subjects with Leber Hereditary Optic Neuropathy due to Mutations in the Mitochondrial ND4 Gene: The REVEAL Study," was published online in BioDrugs.

Read more here:

Gene Therapy GS010 Safe, Well-Tolerated for LHON Patients - MD Magazine

The new gene therapy target,GJB2 coding for the Connexin 26 protein, has been added to Sensorions development portfolio: with the target the third candidate to emerge from the R&D collaboration with Institut Pasteur. It represents the largest gene therapy opportunity for the French biotech to date.

The GJB2 program will focus on major new markets with an estimated patient population of 300,000 children and adults in Europe and the US alone.

Sensorion, a French clinical-stage biotech based in Montpellier, was founded in 2009 to develop novel therapies to restore, treat and prevent hearing loss disorders.

The GJB2 program draws on new research from Institut Pasteur which shows that the same genes that underly congenital deafness are also involved in severe forms of presbycusis (age-related hearing loss). These forms of presbycusis appearing to be monogenic types of hearing loss that can be potentially treated by gene therapy.

Although the types ofGJB2mutations in children and adults may differ, Sensorion says gene therapy could potentially provide a solution to both.

Mutations inGJB2are believed to alter a gap junction protein widely expressed in the inner ear, disturbing intercellular exchanges of molecules and leading to hearing loss that is severe-to-profound in a majority of cases.

Institut Pasteur research now shows three pathologies related to GJB2 mutations: congenital deafness;age-related hearing loss in adults; and progressive forms of hearing loss in children. Sensorion will prioritize the latter two forms, saying it is the first company to address these needs and offering the potential of large market opportunities.

The emergence of a new gene therapy target candidate validates our conviction that long-term solutions for restoring hereditary hearing loss will arise from an in-depth analysis of the "genetic landscape" of hearing loss," saidNawal Ouzren, CEO of Sensorion.

"It was clear that mutations in the GJB2 gene are important in severe to profound childhood hearing loss. However, the new discovery made by our collaborators at Institut Pasteur shows that alteration of this gene in adults offers new opportunities for Sensorion. It marks significant potential expansion of our pipeline and supports our goal of becoming a global leader in the field of gene therapies for hearing loss disorders.

Sensorions collaboration with Institut Pasteur initiated in 2019 has already led to gene therapy candidate programs in two other indications. Its USHER-CT gene therapy development program aims to restore inner ear function for patients suffering from Usher Syndrome Type 1 by providing a healthy copy of the USH1G gene coding for the SANS protein.

Meanwhile, the OTOF-GT gene therapy development program seeks to restore hearing in people with Otoferlin deficiency, one of the most common forms of congenital deafness.

Both of these have been proved in concept in preclinical studies.

See original here:

Sensorion and Institut Pasteur announce new gene therapy collaboration - BioPharma-Reporter.com

Its back to the drawing board for bluebird bio and its discussions with NICE, which has rejected its beta thalassaemia gene therapy Zynteglo for regular NHS use in first draft guidance.

NICE is assessing Zynteglo (betibeglogene autotemcel), a one-off gene therapy for the condition, which can have life-threatening consequences and is associated with a curtailed life expectancy.

There is a curative treatment for people who rely on blood transfusions to survive and maintain their levels of red blood cells.

But haematopoietic stem cell transplantation is only possible when a donor with a matching human leukocyte antigen signature, within the correct age range, is available.

In this first draft guidance NICE raised a series of issues with Zynteglo, which bluebird has already agreed to supply at a confidential discount from its hefty price tag, which is around 1.57 million in Europe.

NICE said that data came from a small sample of patients and is using its standard discount rate of 3.5% to calculate the long-term benefits of the treatment.

The company has unsuccessfully pushed for a rate of 1.5%, which would attach more value to the long-term benefits of the therapy over a patients lifetime.

There was also a long list of other technical issues raised by NICE that count against Zynteglo in the assessment, including costs of fertility preservation and the number of simulated profiles in bluebirds data.

Nicola Redfern, bluebird bios UK general manager, said the first step is to present a new analysis of data addressing issues raised by NICE before there are any discussions about lowering the price again.

She pointed out that the dossier presented to NICE was compiled in 2019 and the company now has six years worth of follow-up data.

Redfern also added that this is the first time that NICE had assessed a gene therapy using its single technology assessment process, which is used for medicines likely to be used more widely on the NHS.

However Redfern was still surprised the rejection given the discussions with NICE so far in the process.

She said: Some of the specifics we thought we had covered off with them and discussed. The thing that baffled me most was the lack of understanding of this disease upon the people living with it.

The UK Thalassaemia Society noted NICEs citation of a UK patient reference report stating that 37% of respondents would immediately accept a referral to a transplant specialist and betibeglogene autotemcel if offered it.

Romaine Maharaj, executive director at UKTS, said: Most of our members are very excited about the new therapy developments and are keen to explore these treatment options.

Bone marrow transplant is only an option for a very small proportion of people with thalassaemia and so gene therapy offers a real potential alternative as a one-off resolution to this life-limiting condition.

See the article here:

bluebird bio 'baffled' after NICE rejects beta-thalassaemia gene therapy - - pharmaphorum

GenSight Biologics has reported that results from the Phase I/IIa REVEAL clinical trial of LUMEVOQ (lenadogene nolparvovec) gene therapy demonstrated a favourable safety profile in individuals with ND4 Leber hereditary optic neuropathy (LHON).

The trial also determined the dose used in the Phase III RESCUE and REVERSE trials.

Launched in 2014, the open-label, single-centre, dose escalation study analysed the safety and tolerability of LUMEVOQ in 15 participants with ND4 LHON who were followed for up to five years after administering a single intravitreal injection to their worst-affected eye.

Participants were enrolled in four cohorts of three subjects each, with each cohort given increasing doses of the gene therapy.

Dose escalation continued only after a safety evaluation by an independent data safety monitoring board (DSMB). A final extension cohort received the dose that the DSMB determined to have the best benefit-risk ratio among those administered to the four previous cohorts.

Data showed that LUMEVOQ was well-tolerated over the follow-up period of five years, with no serious adverse events noted.

These results are the first to show the favourable safety profile of the gene therapy while hinting at the efficacy analysed in the Phase III trials.

This safety profile was then affirmed in the Phase III RESCUE and REVERSE trials.

GenSight co-founder Dr Jos-Alain Sahel said: This study confirms the gene therapys favourable long-term safety and further demonstrates that the trends that were initially observed have been maintained for at least five years.

GlobalData's TMT Themes 2021 Report tells you everything you need to know about disruptive tech themes and which companies are best placed to help you digitally transform your business.

The company noted that REVEAL trial data and analyses were main components of the evidence package submitted to the European Medicines Agency (EMA) last September.

The submission was made seeking Marketing Authorisation Application (MAA) for LUMEVOQ for treating patients with visual loss due to ND4 LHON. The EMA decision is expected in the fourth quarter of this year.

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GenSight Biologics' gene therapy proves safe in LHON trial - Clinical Trials Arena

Dublin, Feb. 15, 2021 (GLOBE NEWSWIRE) -- The "Gene Therapy Market by Therapeutic Approach, Type of Gene Therapy, Type of Vectors Used, Therapeutic Areas, Route of Administration, and Key Geographical Regions: Industry Trends and Global Forecasts, 2020-2030" report has been added to ResearchAndMarkets.com's offering.

Over time, several gene therapies have been developed for the treatment of both simple and complex genetic disorders. In fact, there are 10 approved gene therapies (recent examples include Zolgensma, ZyntegloT and Collategene) to date, and more than a thousand product candidates being evaluated in clinical trials, worldwide. Considering the current pace of research and product development activity in this field, experts believe that the number of clinical research initiatives involving gene therapies are likely to grow by 17% annually. In this context, the USFDA released a notification, mentioning that it now expects to receive twice as many gene therapy applications each year, starting 2020. Despite the ongoing pandemic, it is worth highlighting that gene therapy companies raised approximately USD 5.5 billion in capital investments, in 2020 alone. This is indicative of the promising therapeutic potential of this emerging class of pharmacological interventions, which has led investors to bet heavily on the success of different gene therapy candidates in the long term.

Several technology platforms are currently available for discovery and development of various types of gene therapies. In fact, advances in bioanalytical methods and genome editing and manipulation technologies, have enabled the development of novel therapy development tools/platforms. In fact, technology licensing is a lucrative source of income for stakeholders in this industry, particularly for those with proprietary gene editing platforms. Given the growing demand for interventions that focus on the amelioration of the underlying (genetic) causes of diseases, it is expected that the gene therapy pipeline will continue to steadily expand. Moreover, promising results from ongoing clinical research initiatives are likely to bring in more investments to support therapy product development initiatives in this domain. Therefore, we are led to believe that the global gene therapy market is poised to witness significant growth in the foreseen future.

Story continues

The report features an extensive study of the current market landscape of gene therapies, primarily focusing on gene augmentation-based therapies, oncolytic viral therapies, immunotherapies and gene editing therapies. The study also features an elaborate discussion on the future potential of this evolving market.

Key Questions Answered

Who are the leading industry players engaged in the development of gene therapies?

How many gene therapy candidates are present in the current development pipeline? Which key disease indications are targeted by such products?

Which types of vectors are most commonly used for effective delivery of gene therapies?

What are the key regulatory requirements for gene therapy approval, across various geographies?

Which commercialization strategies are most commonly adopted by gene therapy developers, across different stages of development?

What are the different pricing models and reimbursement strategies currently being adopted for gene therapies?

What are the various technology platforms that are either available in the market or are being designed for the development of gene therapies?

Who are the key CMOs/CDMOs engaged in supplying viral/plasmid vectors for gene therapy development?

What are the key value drivers of the merger and acquisition activity in the gene therapy industry?

Who are the key stakeholders that have actively made investments in the gene therapy domain?

Which are the most active trial sites related to this domain?

How is the current and future market opportunity likely to be distributed across key market segments?

Key Topics Covered:

1. PREFACE

2. EXECUTIVE SUMMARY

3. INTRODUCTION

4. GENE DELIVERY VECTORS

5. REGULATORY LANDSCAPE AND REIMBURSEMENT SCENARIO

6. MARKET OVERVIEW

7. COMPETITIVE LANDSCAPE

8. MARKETED GENE THERAPIES

9. KEY COMMERCIALIZATION STRATEGIES

10. LATE STAGE GENE THERAPIES

11. EMERGING TECHNOLOGIES

12. KEY THERAPEUTICS AREAS

13. PATENT ANALYSIS

14. MERGERS AND ACQUISITIONS

15. FUNDING AND INVESTMENT ANALYSIS

16. CLINICAL TRIAL ANALYSIS

17. COST PRICE ANALYSIS

18. BIG PHARMA PLAYERS: ANALYSIS OF GENE THERAPY RELATED INITIATIVES

19. DEMAND ANALYSIS

20. MARKET FORECAST AND OPPORTUNITY ANALYSIS

21. VECTOR MANUFACTURING

22. CASE STUDY: GENE THERAPY SUPPLY CHAIN

23. CONCLUSION

A Selection of Companies Mentioned Include:

For more information about this report visit https://www.researchandmarkets.com/r/c6r4ih

About ResearchAndMarkets.comResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

Excerpt from:

Global Gene Therapy Market Outlook to 2030 - by Therapeutic Approach, Type of Gene Therapy, Type of Vectors Used, Therapeutic Areas, Route of...

NEW YORK and RESEARCH TRIANGLE PARK, N.C., Feb. 16, 2021 (GLOBE NEWSWIRE) -- Sio Gene Therapies Inc. (NASDAQ: SIOX), a clinical-stage company focused on developing gene therapies to radically improve the lives of patients with neurodegenerative diseases, announced today that the company will present at the 10th Annual SVB Leerink Global Healthcare Conference taking place February 22-26, 2021. Details on the presentation can be found below.

Company management will also participate in one-on-one investor meetings at the conference.

About Sio Gene Therapies

Sio Gene Therapies combines cutting-edge science with bold imagination to develop genetic medicines that aim to radically improve the lives of patients. Our current pipeline of clinical-stage candidates includes the first potentially curative AAV-based gene therapies for GM1 gangliosidosis and Tay-Sachs/Sandhoff diseases, which are rare and uniformly fatal pediatric conditions caused by single gene deficiencies. We are also expanding the reach of gene therapy to highly prevalent conditions such as Parkinsons disease, which affects millions of patients globally. Led by an experienced team of gene therapy development experts, and supported by collaborations with premier academic, industry and patient advocacy organizations, Sio is focused on accelerating its candidates through clinical trials to liberate patients with debilitating diseases through the transformational power of gene therapies. For more information, visit http://www.siogtx.com.

Contacts:

Media

Josephine Belluardo, Ph.D. LifeSci Communications(646) 751-4361jo@lifescicomms.cominfo@siogtx.com

Investors and Analysts

Parag V. Meswani, Pharm.D.Sio Gene Therapies Inc.Chief Commercial Officerinvestors@siogtx.com

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Sio Gene Therapies to Present at the 10th Annual SVB Leerink Global Healthcare Conference - GlobeNewswire

Betibeglogene autotemcel (beti-cel), a one-time gene therapy, enabled durable transfusion independence in most patients with transfusion-dependent -thalassemia (TDT) who were treated across 4 clinical studies.

Of 60 patients enrolled overall, 17 of 22 (77%) treated in the 2 phase 1/2 studies were able to stop packed red blood cell transfusions. In the 2 phase 3 studies, which used a refined manufacturing process resulting in improved beti-cel characteristics, 89% (n = 31/35) of patients with at least 6 months of follow-up achieved transfusion independence for more than 6 months,1 reported Suradej Hongeng, MD, during the virtual 2021 Transplantation & Cellular Therapy Meetings.

The median follow-up after beti-cel infusion in the 4 studies has been 24.8 months (range, 1.1-71.8).

With up to 6 years of follow-up, 1-time beti-cel gene therapy enabled durable transfusion independence in the majority of patients, said Hongeng, from Ramathibodi Hospital of Mahidol University, in Bangkok, Thailand.

Patients who achieved transfusion independence experienced a 38% median reduction in liver iron concentration (LIC) from baseline to month 48. The median reduction in LIC was 59% in patients with a baseline LIC more than 15 mg/g dw. A total of 21 of 37 (57%) patients who achieved transfusion independence have stopped iron chelation for 6 months or longer, with a median duration of 18.5 months from stopping iron chelation to last follow-up.

Erythropoiesis as determined by soluble transferrin receptor level was also improved in transfusion-independent patients. Bone marrow biopsies showed improvement in the myeloid:erythroid ratio.

Beti-cel adds functional copies of a modified form of the -globin (A-T87Q-globin) gene into a patients own hematopoietic stem cells (HSCs) through transduction of autologous CD34+ cells using a BB305 lentiviral vector. Following single-agent busulfan myeloablative conditioning, beti-cel is infused, after which the transduced HSCs engraft and reconstitute red blood cells containing functional adult hemoglobin derived from the gene therapy.

Of the 60 patients treated, 43 were genotype non-/ and 17 were / . The median age at consent was 20 years in the phase 1/2 trials and 15 years in the phase 3 trials. Median LIC at baseline was 7.1 and 5.5 mg Fe/g dw, respectively, and median cardiac T2 was 34 and 37 msec, respectively. The vector copy number was 0.8 in the phase 1/2 trial and 3.0 in the phase 3 study. Additionally, 32t and 78t CD34+ cells were transduced, respectively.

The phase 1/2 studies showed promising results but lower achievement of transfusion independence in patients with the / genotype, leading to a refinement in the manufacturing process, which resulted in a higher number of transduced cells and a higher number of vector copy number, said Hongeng.

The median time to neutrophil engraftment was 22.5 days and the median time to platelet engraftment was 44 days. Lymphocyte subsets were generally within the normal range after beti-cel infusion, which is different from allogeneic stem cell [transplantation], which is probably around 6 months to a year to get complete recovery of immune reconstitution, he said. The median duration of hospitalization was 42 days.

All patients were alive at the last follow-up (March 3, 2020). Eleven of 60 (18%) of patients experienced at least 1 adverse event (AE) considered related or possibly related to beti-cel, the most common being abdominal pain (8%) and thrombocytopenia (5%). Serious AEs were those expected after myeloablative conditioning: veno-occlusive liver disease (8%), neutropenia (5%), pyrexia (5%), thrombocytopenia (5%), and appendicitis, febrile neutropenia, major depression, and stomatitis (3% each).

Of the 7 patients experiencing veno-occlusive liver disease, 3 were of grade 4 and 2 were of grade 3. Two other patients had grade 2 veno-occlusive disease. There were no cases of insertional oncogenesis.

Persistent vector-positive hematopoietic cells and durable HbaT87Q levels supported stable total hemoglobin over time. In phase 3 trials, the median peripheral blood vector copy number was 1.2 c/dg at month 12 and 2.0 c/dg at month 24, and the median total hemoglobin was 11.5 g/dL at month 12 and 12.9 g/dL at month 24.

The weighted average of hemoglobin during transfusion independence in the phase 1/2 trials was 10.4 g/dL, and patients were transfusion-independent for a median of 51.2 months. In the phase 3 studies, the weighted average of hemoglobin during transfusion independence was 11.9 g/dL, and patients were transfusion-independent for a medium 17.7 months.

Hongeng S, Thompson AA, Kwiatkowski JL, et al. Efficacy and safety of betibeglogene autotemcel (beti-cel; LentiGlobin for -thalassemia) gene therapy in 60 patients with transfusion-dependent -thalassemia (TDT) followed for up to 6 years post-infusion. Presented at: 2021 Transplantation & Cellular Therapy Meetings; February 8-12, 2021; virtual. Abstract 1.

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Beti-Cel Gene Therapy Frees Patients With Beta-Thalassemia From Red Blood Cell Transfusions - OncLive

COLUMBUS, Ohio, Feb. 16, 2021 /PRNewswire/ --Forge Biologics Inc., a fully integrated clinical stage gene therapy manufacturing and development company, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track, Orphan Drug, and Rare Pediatric Disease (RPD) designations to FBX-101 for the treatment of patients with Krabbe disease. Forge is now actively recruiting patients for enrollment in the RESKUE phase 1/2 clinical trial of FBX-101, a novel, first-in-human AAV gene therapy for the disease. FBX-101 is the first intraveniousgene therapy program for patients with Krabbe disease and marks a major step forward in building out the company's hybrid model as a gene therapy manufacturing and development engine.

"FDA's decision to grant these designations to our first-in-human investigational gene therapy highlights the urgency of developing a treatment for Krabbe patients," said Timothy J. Miller, Ph.D., CEO, President and Co-Founder of Forge Biologics. "Krabbe is a devastating disease, and it is imperative to develop treatment options like FBX-101 that may address all manifestations of the disease."

Fast Track Designation is given when the FDA determines that a drug demonstrates the potential to address unmet medical needs for a serious or life-threatening disease or condition. This designation is intended to facilitate development and expedite review of drugs to treat serious and life-threatening conditions, and may also allow for priority or rolling review of a company's Biologics License Application (BLA).

The FDA grants Orphan Drug designation to drugs and biological products intended for the treatment of patients with rare diseases that affect fewer than 200,000 people in the United States. RPD designation is granted by the FDA to encourage treatments for serious or life-threatening diseases primarily affecting children 18 years of age and younger and fewer than 200,000 people in the United States. On December 27, 2020, the Rare Pediatric Disease Priority Review Voucher Program was extended by Congress after it was scheduled to sunset in 2020. Under the newly extended RPD program, if FBX-101 is approved by the FDA, Forge Biologics will qualify for a voucher that can be redeemed to receive a priority review of a subsequent marketing application for a different product.

"Infantile Krabbe is a progressive and devastating leukodystrophy," said Jessie Barnum, M.D., AssistantProfessor,Department of Pediatrics,Division of Blood and Marrow Transplantation and Cellular Therapies and Principal Investigator of the FBX-101 trial at UMPC. "FBX-101 is an AAV gene therapy that has shown promising preclinical efficacy in Krabbe animal models of disease by extending survival and improving neuromuscular function when administered early in the disease course."

"The FBX-101 preclinical data brings a new wave of hope to the Krabbe community," said Anna Grantham, Director of Leukodystrophy Care Network Programs at Hunter's Hope. "These FDA designations for FBX-101 underscore a beautiful and collective effort to accelerate the timelines of bringing this potential therapy to patients who urgently need them."

"To see a promising new treatment for Krabbe receive these designations so quickly brings us one step closer to what everyone in our disease community is ultimately working towards: an FDA-approved treatmentfor Krabbe disease to reach the beside of all patients impacted by this disease," said Stacy Pike-Langenfeld, Director of Programs and Administration at The Legacy of Angels Foundation. "Our mission has always been to promote research to develop and enhance treatments for Krabbe disease, so it's very encouraging to see that Forge and FBX-101 have made so much progress in such a short amount of time."

Patients and families can learn more about clinical trials for FBX-101 by visiting https://www.forgebiologics.com/science/#krabbe.

About Krabbe diseaseKrabbe disease is a rare, inherited leukodystrophy affecting approximately 1:12,500 - 100,000 people in the U.S.A. Krabbe disease is caused by loss-of-function mutations in the galactosylceramidase (GALC) gene, a lysosomal enzyme responsible for the breakdown of certain types of lipids such as psychosine. Without functional GALC, psychosine accumulates to toxic levels in cells. The psychosine toxicity is most severe in the myelin cells surrounding the nerves in the brain and in the peripheral nervous system, eventually leading to the death of these cells. The disease initially manifests as physical delays in development, muscle weakness and irritability and advances rapidly to difficulty swallowing, breathing problems, cognitive, vision and hearing loss. Early onset or "Infantile", Krabbe disease cases usually results in death by age 2-4 years, while later onset or "Late Infantile" cases have a more variable course of progressive decline. There is currently no approved treatment for Krabbe disease.

About FBX-101Forge is developing FBX-101 to treat patients with infantile Krabbe disease. FBX-101 is an adeno-associated viral (AAV) gene therapy that is delivered after a hematopoietic stem cell transplant. FBX-101 delivers a functional copy of the GALC gene to cells in both the central and peripheral nervous system. FBX-101 has been shown to functionally correct the central and peripheral neuropathy and correct the behavioral impairments associated with Krabbe disease in animal models, and to drastically improve the lifespan of treated animals. This approach has the potential to overcome some of the immunological safety challenges observed in traditional AAV gene therapies.

About Forge BiologicsForge Biologics is a hybrid gene therapy contract manufacturing and therapeutic development company. Forge's mission is to enable access to life changing gene therapies and help bring them from idea into reality. Forge has a 175,000 ft2 facility in Columbus, Ohio, "The Hearth", to serve as their headquarters. The Hearth is the home of a custom-designed cGMP facility dedicated to AAV viral vector manufacturing and will host end-to-end manufacturing services to accelerate gene therapy programs from preclinical through clinical and commercial stage manufacturing.By taking a patients-first approach, Forge aims to accelerate the timelines of these transformative medicines for those who need them the most.

For more information, please visit https://www.forgebiologics.com.

Patient, Pediatrician, Genetic Counselors & Family InquiriesDr. Maria EscolarChief Medical OfficerForge Biologics Inc.medicalaffairs@forgebiologics.com

Media Inquiries:Dan SalvoDirector of Communications and Community DevelopmentForge Biologics Inc.media@forgebiologics.com

Investor Relations and Business DevelopmentChristina PerryVice President, Finance and OperationsForge Biologics Inc.Investors@forgebiologics.com

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SOURCE Forge Biologics

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Forge Biologics Receives FDA Fast Track, Orphan Drug, and Rare Pediatric Disease Designations for FBX-101 Gene Therapy for Patients with Krabbe...

Close to a year after Maryland-based CDMO Vigene Biosciences cut the ribbon on its headquarters, spiking demand for cell and gene therapy has prompted the company to lay out a major manufacturing upgrade in its home state.

Vigene is picking up a lease for 52,000 square feet of manufacturing space in Montgomery County, Maryland, situated near its existing headquarters in Rockville. The expansion is set to bring the company's total lab and production space up to 110,000 square feet and, by 2025, will see up to 245 new hires join Vigene's current workforce of 125.

The new facility, located at 14200 Shady Grove Road, will complement existing R&D and manufacturing operations at Vigene's home base as the company faces growing demand for its cell and gene therapy products. Vigene's expansion has snared some financial perks from the state, too, including a $1,225,000 loan from the Maryland Department of Commerce, which is contingent on job creation and capital investment.

Innovation in Rare Disease: Making Progress with Cell & Gene Therapies A Webinar Series from the Rare Disease Innovations Institute and Syneos Health

Join patients and their families, legislators, industry experts, advocates and sponsors to discuss education initiatives, recent advancements and the future promise of cell and gene medicine, and current patient experiences with these therapies.

RELATED: Cognate beefs up cell, gene therapy manufacturing with new plants in U.S., EU

The company is keeping its own spending on the site under wraps, Jeffrey Hung, Ph.D., chief commercial officer of Vigene, said over email. "It suffices to say that we are going to invest heavily on the facility to qualify and commission it for commercial production purpose," he added.

With the new site, Vigene will add five more GMP suites to the 10 it operates now, Hung said. Specifically, the company plans to commission and set up two 2,000-liter single-use bioreactor suites, where upstream and downstream production trains will be located on the same floor for commercial viral vector production. Another floor will house multiple large-scale fermenters for commercial plasma production, he said.

Formed in 2012, Vigene specializes in gene therapies for patients with cancers and serious genetic disorders. It develops, manufactures and distributes adeno-associated viruses, lentiviruses, retroviruses, adenoviruses and plasmid viral vectors for gene delivery.

RELATED: Fujifilm continues CMDO expansion spree with $76M in funding for new Boston site

The company has checked into the COVID-19 fight, too, signing on to produce clinical materials for Maryland compatriot Altimmune's nasal vaccine candidate. Vigene in July agreed to churn out both drug substance and drug product for studies on the vaccine, which registered for a phase 1 trial in late December.

On Dec. 23, Altimmune revealed the FDA had slapped the investigational new drug application for its vaccine, AdCOVID, with a clinical hold, citing the need for protocol modifications and additional chemistry, manufacturing and control data. The company responded to the hold and, at the time, said it didn't expect the move to significantly disrupt its clinical timeline.

Altimmune has also added Swiss CDMO Lonza as a production partner on its nasal vaccine, and it previously set the goal to crank out at least 100 million AdCOVID doses in 2021.

Meanwhile, Vigene's expansion comes shortly after the christening of its Rockville HQ. It was just a year ago that we cut the ribbon at Vigenes new custom-built headquarters and already the growing demand for its gene and cellular therapy products requires additional physical expansion, Benjamin Wu, CEO and president of the company, said in a release.

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CDMO Vigene plots cell and gene therapy manufacturing expansion, adding 245 new jobs along the way - FiercePharma