Moderna's mRNA Drug Joins FDA Rare Disease Accelerator

Moderna has announced that the FDA has chosen its investigational therapy, mRNA-3705, for the Support for Clinical Trials Advancing Rare Disease Therapeutics (START) pilot program. Introduced in September 2023, START aims to facilitate drug development for rare diseases through enhanced communication between the FDA and drug developers. This initiative provides guidance on trial design, control group selection, and patient population, as well as product characterization and the use of non-clinical data to support therapeutic candidates.

Eligibility for START is limited to gene or cell therapies targeting neurodegenerative or genetic metabolic rare diseases that are likely to cause significant disability or death within the first decade of life. Moderna's mRNA-3705, which addresses methylmalonic acidemia (MMA), meets these criteria. MMA is a rare and life-threatening metabolic disorder characterized by the accumulation of toxic substances in the body, leading to metabolic crises and multi-organ damage. Diagnosed typically within the first few months of life, MMA presents a high mortality and morbidity burden and currently lacks approved treatments.

The majority of MMA cases result from a deficiency in the MUT enzyme, which is essential for breaking down amino acids and fatty acids in the mitochondria. Moderna's mRNA-3705 aims to correct this deficiency by delivering a MUT-encoding mRNA molecule encapsulated in a proprietary lipid nanoparticle via intravenous administration.

The FDA has previously granted mRNA-3705 Orphan Drug, Rare Pediatric Disease, and Fast Track designations. Currently, the therapy is being tested in a Phase I/II open-label study involving patients aged one year and older. Kyle Holen, head of development for therapeutics and oncology at Moderna, expressed excitement and pride about the selection of mRNA-3705 for START, noting that it will enhance communication with the FDA and expedite the development program. Moderna plans to initiate a pivotal study for mRNA-3705 this year.

Holen highlighted that this selection underscores the potential of Moderna's mRNA platform beyond vaccines and its promise in addressing serious and unmet medical needs in MMA. Moderna joins four other biopharmaceutical companies chosen for START, which made similar announcements this week.

Denali Therapeutics is participating in START with its investigational enzyme replacement therapy for mucopolysaccharidosis type IIIA. Grace Science’s gene therapy GS-100 for NGLY1 deficiency is also included in the program. Additionally, Larimar Therapeutics' novel protein replacement therapy nomlabofusp for Friedrich’s ataxia and Neurogene’s developmental gene therapy NGN-401 for Rett syndrome have been selected for START.