MDA Kickstart Program for drug development for extremely rare neuromuscular diseases launched

MDA Kickstart Program for drug development for extremely rare neuromuscular diseases launched

Collaboration with UC Davis
Production partnership with Forge Biologics

New York, September 9, 2024 – The Muscular Dystrophy Association (MDA) today announced a new research program called MDA Kickstart for Ultra Rare Neuromuscular Diseases. The MDA Kickstart program is a collaborative internal project to develop gene therapies for select ultra-rare genetic diseases that may not have significant commercial value. The program was developed as a strategy and operational solution to de-risk the development of gene therapies for ultra-rare neuromuscular diseases and aims to bridge the translational gap between early academic science, regulatory approval, access and utilization.

“The Muscular Dystrophy Association recognizes that many neuromuscular diseases are too rare to be commercially attractive for therapy development by pharmaceutical companies. The new MDA Kickstart program is an internal gene therapy program that works with academic, corporate and community groups to advance these therapies by creating economies of scale and improving the evaluation of these therapies. The MDA Kickstart program will help ensure that patients with extremely rare forms of neuromuscular diseases are not left out in the era of genetic medicine and can also benefit from the potential advantages of gene therapies,” said Sharon, Hesterlee, PhD, Principal Investigator, MDA.

The selection of the first MDA Kickstart project was guided by external advisors, including leading scientists and industry experts in gene therapy. They reviewed the proposals and recommended a genetic disease with high unmet need and high potential to benefit from a gene therapy approach. Adeno-associated virus (AAV) gene replacement therapy has proven to be a viable strategy to treat the underlying genetic cause of numerous neuromuscular diseases (NMDs). While industry interest in supporting translational trials for AAV-based gene therapies is increasing, these have been limited to more common NMD subtypes, and commercial interest in indications affecting fewer than 1000 people in the U.S. is minimal. MDA's Kickstart program will seek to develop strategies and operational solutions to reduce the hurdles and de-risk translation of gene therapies for ultra-rare NMDs.

“Currently, an estimated 95% of patients with rare diseases have no approved or developmental therapy. We need a medical device paradigm that serves all patients regardless of the rarity of the disease. The MDA Kickstart program is critical to finding an ethical, efficient and implementable solution that addresses the existing unmet needs of people with extremely rare neuromuscular diseases,” said Marina Kolocha, PharmD, PhD, PMP, Program Manager, MDA Kickstart Program.

Collaboration with UC Davis

The first MDA Kickstart project, developed by Ricardo A. Maselli, MD, Professor, Neurology, Clinical Neuroscience, University of Californiawill focus on developing a gene therapy for a form of congenital myasthenic syndrome (CMS) caused by mutations in the CHAT Gene that encodes the enzyme choline acetyltransferase. This enzyme is required for the synthesis of the neurotransmitter acetylcholine. If it is defective, it disrupts the transmission of electrical signals from the nerves to the muscles and leads to muscle weakness and potentially fatal respiratory arrest. It is estimated that around 200 children and adults in the USA are affected by this disease. It is characterized by muscle weakness and life-threatening respiratory arrest.

Dr. Maselli is a world-recognized expert in the field of congenital myasthenic syndromes. MDA will work with Dr. Maselli and his team to build a platform of resources and personnel to produce a complete preclinical data package for submission to the FDA (US Food and Drug Administration) for a formal Pre-IND (Investigational New Drug) meeting – an early milestone on the path to FDA approval for a clinical trial.

“CMS due to CHAT Mutations are a serious disease because there is a risk of sudden, potentially fatal respiratory arrest. If suspected, this disease can be easily diagnosed in newborns and infants through genetic blood tests. Unfortunately, in many cases the disease remains undetected until adulthood,” said Dr. Maselli.

The MDA Kickstart collaborative team consists of internal, trusted vendors and external experts to advance the selected project to the pre-IND approval milestone in collaboration with Dr. Maselli and other members of UC Davis, including their Stem Cell and Gene Therapy Centers with Jan Nolta, PhD, Director, and the Office of Sponsored Research with Rajagopal Gururajan, IP Officer. Dr. Kolocha brings expertise in developing gene therapies for ultra-rare diseases and regulatory expertise to serve as program manager for the MDA Kickstart program.

“Our team at the UC Davis Institute for Regenerative Cures has worked closely with Dr. Maselli over the past decade, and we are continually impressed by her immense commitment to patients with rare neuromuscular diseases,” said Nolta, PhD, professor Institute for Regenerative Medicine, UC Davis Health“It is wonderful to now be working with the impressive team at MDA to accelerate the development of therapies into the clinic for these patients who have few other options.”

Production partnership with Forge Biologics

MDA has partnered with Forge Biologics to provide AAV processing and analytical development manufacturing services for the MDA Kickstart program. The program will utilize Forge's platform process including its proprietary HEK293 Suspension Ignition Cells™ and pEMBR™ adenovirus helper plasmid. All development and manufacturing activities will take place at Hearth, Forge's 18,580 square foot facility in Columbus, Ohio.

“Collaborating with the Muscular Dystrophy Association embodies our mission at Forge to bring potentially life-changing treatments to patients with rare diseases,” said JOhn Maslowski, Chief Commercial Officer at Forge Biologics“We are excited to support the MDA Kickstart program and bring these important projects into the next phase of development.”

Renewal of the FDA Priority Review Voucher for Rare Pediatric Diseases

MDA's applications for Orphan Drug and Rare Childhood Disease designation for this program are currently under review by the FDA. Importantly, approval of the latter designation will confirm this program's eligibility to receive a Priority Review Voucher (PRV) for Rare Childhood Diseases following FDA marketing approval. However, this can only be implemented if the Rare Childhood Disease PRV program is re-approved.

“The MDA Kickstart program and our efforts to develop a gene therapy for congenital myasthenic syndrome (CMS) caused by mutations in the CHAT gene are exactly the kind of programs that build on the Priority Review Voucher for rare pediatric diseases and encourage for-profit biopharmaceutical companies to bring these therapies to market,” said Paul Melmeyer, Executive Vice President, Public Policy and Advocacy, MDA“That's why the PRV program for rare childhood diseases must be extended beyond September 30th and a long-term re-approval must be obtained by the end of the year. We encourage our community to join us in pushing for this re-approval here.”

About the Muscular Dystrophy Association

The Muscular Dystrophy Association (MDA) is the largest voluntary health organization in the United States for people with muscular dystrophy, ALS, and over 300 related neuromuscular diseases. For nearly 75 years, MDA has been a leader in accelerating research, improving care, and advancing support for our families. MDA's mission is to enable the people we care for to live longer, more independent lives. For more information, visit mda.org and follow MDA on Instagram, Facebook, XThreads, TikTok, LinkedIn and YouTube.

About the UC Davis Institute for Regenerative Cures

UC Davis is a leader in regenerative medicine. Nearly 150 scientists work on a variety of stem cell-related research projects at the Davis and Sacramento campuses. The UC Davis Institute for Regenerative Cures, a facility supported by the California Institute for Regenerative Medicine (CIRM), opened on the Sacramento campus in 2010. This $62 million facility is the university's center for stem cell research. It includes Northern California's largest academic Good Manufacturing Practice laboratory with state-of-the-art equipment and manufacturing space for cell and gene therapies. UC Davis also has a joint facility for translational human embryonic stem cell research in Davis and collaborates with the Institute for Pediatric Regenerative Medicine at Shriners Hospital for Children Northern California. All programs and facilities complement the university's Clinical and Translational Science Center and focus on turning stem cells into cures. Learn more here.

About Forge Biologics

Forge Biologics, a member of Ajinomoto Bio-Pharma Services, is a company specializing in contract manufacturing of hybrid gene therapies and clinical-stage therapeutics development, enabling access to life-changing gene therapies by taking them from concept to reality. Headquartered in Columbus, Ohio, Forge's 18,580 square foot facility, “The Hearth,” is home to 20 custom-designed cGMP suites with 200,000 liters of production capacity. Forge's end-to-end, scalable plasmid and AAV manufacturing services include research-grade manufacturing, process and analytical development, cGMP manufacturing, fill and finish, and integrated regulatory support to accelerate timelines for breakthrough medicines for patients with genetic diseases. For more information, visit www.forgebiologics.com.