The FDA's Support for Clinical Trials Advancing Rare Disease Therapeutics (START) program, an initiative modeled after Operation Warp Speed, has selected its first pilot program candidates, aiming to accelerate the development of therapies for rare diseases. This program seeks to address the unique challenges associated with rare disease drug development and expedite the regulatory process.
Initial Therapies Selected
Denali Therapeutics, Neurogene, Larimar Therapeutics, and Grace Science are the first companies to benefit from the FDA's enhanced guidance and advice. This support will cover areas such as clinical trial design, patient population selection, use of nonclinical information, and product characterization. The pilot program is expected to eventually include six or more projects.
Denali Therapeutics: DNL12 for MPS IIIA
Denali's candidate, DNL12, is an enzyme replacement therapy (ERT) for mucopolysaccharidosis (MPS) IIIA, also known as Sanfilippo syndrome type A, a form of lysosomal storage disease. DNL12 is currently in a phase 1/2 trial. MPS IIIA is a devastating neurodegenerative disease with no FDA-approved treatment, and the average lifespan of patients is around 15 years. Prior attempts to develop therapies for MPS IIIA, including bone marrow transplants, have yielded disappointing results.
Neurogene: NGN-401 for Rett Syndrome
Neurogene's contribution is NGN-401, a gene therapy for Rett syndrome, a rare genetic neurological disorder primarily affecting girls. This condition leads to severe impairments in brain development. NGN-401 is in a phase 1/2 trial, with preliminary safety data already available and initial efficacy results expected before the end of the year. While Acadia Pharmaceuticals’ Daybue (trofinetide) is approved for Rett syndrome at a cost of $375,000 per year, Neurogene’s approach offers a potential one-time alternative if successful.
Larimar Therapeutics: Nomlabofusp for Friedreich's Ataxia
Larimar is participating with its nomlabofusp, a protein replacement therapy for Friedreich’s ataxia (FA), a progressive disease caused by mutations leading to low levels of frataxin, a protein crucial for mitochondrial function. Nomlabofusp is designed to deliver frataxin to mitochondria and has shown positive top-line results in a phase 2 study, with a regulatory filing anticipated in the latter half of next year. Last year, the FDA approved Biogen’s Skyclarys (omaveloxolone) as the first treatment for FA, priced at $370,000 per year.
Grace Science: GS-100 for NGLY1 Deficiency
Grace Science’s GS-100 gene therapy for NGLY1 deficiency has been included in START, following the treatment of a second patient in the initial part of a phase 1/2/3 study. A third patient is scheduled to be treated at a higher dose later this summer. NGLY1 deficiency is a severe, life-threatening disease with no approved therapy, causing developmental delay, cognitive impairment, movement disorders, and other neurological symptoms.
The FDA launched START with the goal of facilitating more efficient development of potentially life-saving therapies for rare disease indications and helping sponsors generate high-quality data to support future marketing applications.
