Category Archives: Genetic Therapy

It turns out a regulatory delay isnt the only bump on Sareptas road to gene therapy glory.

The biotech is being sued by Regenxbio, which is alleging that its slate of gene therapy programs, including two for Duchenne muscular dystrophy and limb-girdle muscular dystrophy infringes on a patent originally owned by the University of Pennsylvania.

The lawsuit, which was first reported by Bloomberg Law, adds another wrinkle as Sarepta strives to stay in the lead in a race to deliver the first genetic fix for Duchenne muscular dystrophy. After making its name with two antisense drugs neither of which has been proven to have an effect against the crippling disease the Cambridge, MA-based biotech has been viewed as the frontrunner versus Pfizer and trouble-prone Solid Bio. Roche was impressed enough to pay $1.15 billion to acquire ex-US rights to the program.

But Regenxbio wants Sarepta to stop stepping on their patents and pay up. The biotech, which is now based in Rockville, MD, is seeking damages for past, present and/or future infringement equaling no less than a reasonable royalty.

At the center of the dispute is US Patent No. 10,526,617. Jim Wilson, the gene therapy luminary who co-founded Regenxbio, was cited as an inventor on that patent, granted this January.

As it covers a cultured host cell containing a recombinant nucleic acid molecule encoding the capsid protein, the technology can be used to create adeno-associated vectors both in animal studies and for delivering a transgene into humans.

The vectors made using the claimed subject matter of the 617 Patent have unique properties, e.g., an ability to target certain types of cells in the body, the lawsuit states.

Specifically, Regenxbio alleges, Sareptas Duchenne program SRP-9001 is manufactured by a process that includes making and using a cultured host cell a recombinant nucleic acid molecule encoding an AAVrh74 vp1 capsid protein. The same capsid protein is also integral to SRP-9003, the limb girdle candidate, and a host of other follow-on gene therapies.

Regenxbio is suing as Sarepta is sorting out a new request from regulators that can push back its pivotal study for Duchenne. While CEO Doug Ingram assured investors that quality control issues such as this are not uncommon and pinned the delay on an overburdened FDA, he stopped short of promising concrete timelines.

Focused on retinal, metabolic and neurodegenerative diseases for its internal pipeline, Regenxbio is perhaps more accomplished as a gene therapy tech provider. Novartis and Abeona have both licensed its NAV tech platform.

It also doesnt shy away from legal actions. In its most recent quarterly report, Regenxbio disclosed that Abeona failed to make a $8 million payment due in April, effectively terminating their licensing agreement. In response to an arbitration claim Abeona filed in May alleging we breached certain responsibilities to communicate with Abeona regarding our prosecution of licensed patents, Regenxbio filed a counterclaim to ask for $28 million including $20 million that would have been owed under the pact.

Last November Regenxbio challenged the FDAs arbitrary and capricious decisions to issue a full clinical hold on its diabetic retinopathy trial and a partial hold on wet age-related macular degeneration. The company had withdrawn the IND for diabetic retinopathy, and the FDA lifted the partial hold for wet AMD two months later.

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Sarepta faces another gene therapy hiccup as Regenxbio sues over Jim Wilson's patent - Endpoints News

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Gene therapies are set to revolutionise healthcare by treating diseases at the genetic level. They address the underlying cause of disease and can restore a patient to normal or near normal health. As one-time, personalised treatments, gene therapies have the potential to transform current care pathways by offering eligible patients durable outcomes when successful.

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They offer a one-time intervention, when often the alternative is decades of chronic treatment and monitoring, benefitting both patients and carers. Health and social care systems could also benefit, when complex chronic care regimes can be eliminated or greatly reduced, with significant resources re-deployed across the health and social care system; pertinent in a post-covid-19 world. Of course, gene therapy, as well as the procedure needed to prepare patients to receive it, can have serious side effects and there must be a rigorous assessment of potential risks and benefits to identify the right patients for the treatment.

Additionally, the cost-effectiveness of gene therapies, depends very much on their capacity of delivery health and social savings over a patients lifetime. As many patients treated with gene therapies will be children and young adults, the treatment may deliver additional societal gains over decades.

There are currently over 950 companies worldwide developing Advanced Therapy Medicinal Products, with therapies being tested in 1052 clinical trials, as of Q3 2019.1 Many of these are gene therapies that may become available in the UK over the next five years.

Provision needs to be made urgently for aligned regulatory assessment, health technology appraisal and NHS managed introduction, both in terms of infrastructure as well as reallocated budget. Life science companies also have a responsibility to set value-based prices and should consider alternative payment models and risk share agreements in collaboration with the NHS and government to further ensure value and affordability.

Gene therapies are positive and disruptive technologies that require whole system change to ensure that a post-Brexit NHS is at the forefront of provision rather than lagging behind its European neighbours. There is a window of opportunity for the MHRA with renewed responsibilities in 2021, as well as the National Institute for Health and Care Excellence currently conducting its Methods Review to ensure both regulatory and appraisal systems are aligned for optimal assessment of modern medicines, including gene therapies.

NICEs review of the methods is highly significant as it will set the framework for how England and Wales will provide access to new and breakthrough medicines. Areas of focus should include wider recognition of gene therapies and their benefits, including the one-off treatment offer to patients, gains to the health and social care system, plus pragmatic ways to address inherent lifetime uncertainty.

Crucially, for paediatric and young adult patients, there is an additional challenge the NICE methods review needs to resolve. High economic discount rates used in the health economic assessment process by NICE has a prejudicial impact on the cost-effectiveness of treatments that are intended to offer benefits over decades, such as gene therapies. This issue can be easily addressed if Treasury guidance for utilising lower discount rates is adopted.

A successful NICE Methods Review would ensure that the UK has a fit-for-purpose medicines assessment process. This will help to achieve world-leading status for bringing new medicines such as gene therapy to patients and will sustain UK-based research and development investment. This should be prioritised as the end of the EU exit transition period approaches, to ensure the governments vision of a vibrant post-Brexit economy, fuelled by science and technology, allows the UK to lead the world in healthcare innovation.

1. Alliance for Regenerative Medicine. Quarterly regenerative medicine sector report Q3. 2019. Available at: https://alliancerm.org/?smd_process_download=1&download_id=5556 [Accessed 11 February 2020].

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Gene Therapy will the NHS lead or follow? - Health Service Journal

BEDFORD, Mass., Sept. 18, 2020 (GLOBE NEWSWIRE) -- Homology Medicines, Inc. (Nasdaq: FIXX), a genetic medicines company, announced today participation and presentations at the following virtual conferences:

The live webcast presentations from the Oppenheimer and Chardan conferences will be accessible on Homologys website in the Investors section, and the webcast replays will be available on the website for 90 days following the presentations. For on-demand webcasts from the Cell & Gene Meeting on the Mesa conference, please visit http://www.meetingonthemesa.com for full information.

About Homology Medicines, Inc. Homology Medicines is a genetic medicines company dedicated to transforming the lives of patients suffering from rare genetic diseases with significant unmet medical needs by curing the underlying cause of the disease. Homologys proprietary platform is designed to utilize its human hematopoietic stem cell-derived adeno-associated virus vectors (AAVHSCs) to precisely and efficiently deliver genetic medicinesin vivoeither through a gene therapy or nuclease-free gene editing modality across a broad range of genetic disorders. Homology has a management team with a successful track record of discovering, developing and commercializing therapeutics with a particular focus on rare diseases, and intellectual property covering its suite of 15 AAVHSCs. Homology believes that its compelling preclinical data, scientific expertise, product development strategy, manufacturing capabilities and intellectual property position it as a leader in the development of genetic medicines. For more information, please visitwww.homologymedicines.com.

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Homology Medicines to Participate in Upcoming Conferences - GlobeNewswire

DetailsCategory: DNA RNA and CellsPublished on Monday, 14 September 2020 17:17Hits: 589

Preclinical data published today in Nature Biomedical Engineering shows reversal of disease phenotypes indicating potential of RNA-targeting systems as treatments for DM1 and other RNA mediated diseases

SAN DIEGO, CA, USA I September 14, 2020 I Locanabio, Inc., a leader in RNA-targeted gene therapy, today announced that results from a preclinical study of the company's therapeutic systems for the potential treatment of myotonic dystrophy type 1 (DM1) were published in Nature Biomedical Engineering. For the full article, titled "The sustained expression of Cas9 targeting toxic RNAs reverses disease phenotypes in mouse models of myotonic dystrophy," please visit: https://www.nature.com/articles/s41551-020-00607-7

Scientists at Locanabio, working with academic collaborators at UC San Diego School of Medicine and the University of Florida, assessed whether an RNA-targeting CRISPR Cas9 system (RCas9) could provide molecular and functional rescue of dysfunctional RNA processing in a DM1 mouse model. The RCas9 system was administered with one dose of an AAV gene therapy vector. Results in both adult and neonatal mice and using both intramuscular and systemic delivery showed prolonged RCas9 expression even at three months post-injection with efficient reversal of molecular (elimination of toxic RNA foci, MBNL1 redistribution, reversal of splicing biomarkers) and physiological (myotonia) features of DM1.Importantly, there were no significant adverse responses to the treatment.

"These results are consistent with earlier findings from several in vitro studies in muscle cells derived from DM1 patients published by Locanabio's scientific co-founder Dr. Gene Yeo of UC San Diego and further indicate the significant potential of our RNA-targeting gene therapy as a DM1 treatment," said Jim Burns, Ph.D., Chief Executive Officer at Locanabio. "Data show that our RNA-targeting system is able to destroy the toxic RNA at the core of this devastating genetic disease and thereby correct the downstream molecular and biochemical changes that result in myotonia, which is a hallmark symptom of DM1. We are pleased that Nature Biomedical Engineering recognizes the value of these preclinical data and we look forward to further advancing this developmental program to the benefit of DM1 patients."

"Currently available treatments for DM1 can improve specific symptoms but do not target the underlying biology and cause of the disease. These data demonstrate that RNA-targeting systems may efficiently and specifically eliminate toxic RNA repeats that cause DM1 and potentially lead to a more effective treatment option for patients," said Dr. Yeo. "The results also indicate that RNA-targeting gene therapy has potential applications in the treatment of other diseases, such as Huntington's disease and certain genetic forms of ALS, which are also caused by a buildup of toxic RNA repeats."

These studies were funded in part by the Muscular Dystrophy Association (MDA). "We are delighted to support Locanabio's recent work in myotonic dystrophy. These preclinical results represent a promising advance and a novel scientific approach for a group of patients who represent a major unmet medical need," said Sharon Hesterlee, Ph.D., Chief Research Officer, MDA.

About Locanabio, Inc.

Locanabio is the global leader in developing a new class of genetic medicines. Our unique and multi-dimensional approach uses gene therapy to deliver RNA binding protein-based systems to correct the message of disease-causing RNA and thereby change the lives of patients with devastating genetic diseases. These broad capabilities delivered via gene therapy enable Locanabio to potentially address a wide range of severe diseases with a single administration. The company is currently advancing programs in neuromuscular, neurodegenerative and retinal diseases. For more information, visit http://www.locanabio.com.

About Myotonic Dystrophy

Myotonic dystrophy type 1 (DM1) is an autosomal dominant genetic disorder affecting skeletal muscle, cardiac muscle, the gastrointestinal tract, and the central nervous system. DM1 is caused by a mutation in the myotonic dystrophy protein kinase (DMPK) gene. This mutation leads to a repeat expansion of the CTG (cytosine-thymine-guanine) trinucleotide. The expanded CTG is transcribed into toxic CUG (cytosine-uracil-guanine) repeats in the DMPK messenger RNA (mRNA). These toxic mRNA repeats lead to disease symptoms including progressive muscle wasting, weakness and myotonia (delayed relaxation of skeletal muscle), a hallmark of DM1. The incidence of myotonic dystrophy has historically been estimated at one in 8,000 individuals worldwide or approximately 40,000 people in the United States.

SOURCE: Locanabio

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Treatment with RNA-Targeting Gene Therapy Reverses Molecular and Functional Features of Myotonic Dystrophy Type 1 in Mice | DNA RNA and Cells | News...

The European Medicines Agency is on the verge of releasing revised guidance for advanced therapy medicinal products containing genetically modified cells, which includes chimeric antigen receptor (CAR)-T cell therapies.

The Guideline on quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells was originally issued in 2012 but underwent revision and consultation from July 2018-July 2019. The revised version is expected to be adopted in October and published in November, according to Ana Hidalgo-Simon, MD, PhD, head of advanced therapies at EMA. She previewed the major changes at RAPS Convergence 2020.

There were an enormous number of comments on the document, Hidalgo-Simon said.The agency is also working on a Q&A document on principles of good manufacturing practices (GMP) for Advanced Therapy Medicinal Products (ATMP) starting material. There will likely be consultation on the document in 2021, she said. (RELATED: Regulation of advanced therapy medicinal products in the EU, Regulatory Focus, 16 July 2020.)

Major changesEMA chose to update the guidance to reflect the increase in clinical experience with these therapies, particularly chimeric antigen receptor-T (CAR-T) cells; to cover new categories of products, such as induced pluripotent stem (iPS) cells; and to allow for consideration of new tools for genetic modification of cells, such as genome editing technologies, she said.

The main quality updates are related to starting materials, the manufacturing process, and characterization and release. For example, the starting materials guidance will now include genome editing tools, while the manufacturing process includes a new section on comparability. The characterization and release portion of the guidance includes specific advice for CAR-T cells.

Additionally, the guidance calls for dose-finding studies to explore safety, toxicity, and anti-tumor activity at different dose levels, to define the threshold dose required for anti-tumor effect, and to define the recommended dose or range for Phase 2 studies. She said sponsors need to show a solid rationale for the criteria being used to find the dose.

The guidance also calls for Phase 3 confirmatory trials to follow a randomized controlled design, comparing the CAR-T cell therapy to a reference regimen, unless otherwise scientifically justified. Single-arm studies will continue to be allowed, but they will be the exception, Dr. Hidalgo-Simon said.

Be very careful with the design of the trials, she advised. The assumptions need to be really, very well backed.

When it comes to safety, the guidance calls for a 15-year follow period. While sponsors wont have all the answers at the time of submission, Hidalgo-Simon said they should have a plan that includes monitoring during the post-authorization period.

Hidalgo-Simon also advised sponsors to think beyond the approval process and consider what evidence will be needed to convince other stakeholders -- from patients to payers -- about the safety and efficacy of the therapy.

Avoiding development pitfallsRichard Dennett, PhD, the senior director of chemistry, manufacturing and controls regulatory affairs at PPD, also participated in the RAPS Convergence 2020 session on advanced therapies. He reviewed development points where companies can run into trouble with advanced therapies, particularly CAR-T cell products.Dennett recommended that product sponsors keep the end in mind when developing advanced therapies by focusing on the target product profile at the beginning of development. That profile includes the indication for which approval will be sought and the incidence of that indication; other considerations include mode of action, demographics, how much of the product needs to be produced, and market access and reimbursement considerations.

He also outlined several areas where developers should focus to create a watertight regulatory package, including sufficient product characterization, potency assay, impurities, formulation, stability, lack of sufficient development batches, and validation strategy.

Dennett urged developers to dive into the growing number of regulatory guidance documents for advanced therapies. In addition to the European guidance documents, developers should consultthe US Food and Drug Administrations Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs), which was released in January 2020. (RELATED: Advanced therapies: Trip hazards on the development pathway, Regulatory Focus, 02 August 2020)

Live and breathe the guidances that are out there, Dennett advised. They allow us to understand what expectations we need to meet.

The key to success in advancing CAR-T cell therapies is the mitigation of risk, Dennett said: The biggest risk is the one that you havent thought of.RAPS 2020 Convergence

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Convergence: EMA close to finalizing guidance for advanced therapies - Regulatory Focus

Abeona Therapeutics (NASDAQ: ABEO) shares are trading higher on Friday after B. Riley FBR initiated coverage on the stock with a Buy rating and announced a price target of $5 per share.

Abeona Therapeutics is a clinical-stage biopharmaceutical company. The firm is focused on developing gene therapies and plasma-based products for life-threatening rare genetic diseases. The gene therapy involves the use of DNA as a potential therapy to treat a disease.

The company's initial programs are focused on lysosomal storage diseases such as Mucopolysaccharidosis (MPS) IIIA and IIIB. It is also developing ABO-202 and ABO-201, which are AAV-based gene therapies for the CLN1 and CLN3 forms of Batten Disease, respectively, ABO-401 for the treatment of cystic fibrosis, and ABO-50X for the treatment of retinal diseases.

Abeona Therapeutics shares were up 14.80% at $2.25 at the time of publication on Friday. The stock has a 52-week high of $5.19 and a 52-week low of $1.35.

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Why Abeona Therapeutics Is Trading Higher Today - Yahoo Finance