Center for Biologics Evaluation and Research has chosen mRNA-3705 as one of four investigational medicines for accelerated development to address unmet medical needs for rare diseases

Moderna, Inc. announced that the U.S. Food and Drug Administration (FDA) has selected mRNA-3705 for the Support for Clinical Trials Advancing Rare Disease Therapeutics (START) pilot program. mRNA-3705 is an investigational therapeutic for methylmalonic acidemia (MMA) due to methylmalonic-CoA mutase (MUT) deficiency.

"We are excited about this opportunity and proud that our investigational mRNA therapeutic for MMA was selected by the U.S. FDA for the START pilot program. This selection highlights the promise of Moderna's innovative mRNA platform beyond vaccines and the potential this novel medicine may have in addressing the serious and unmet medical needs of MMA," said Kyle Holen, M.D., Moderna's Senior Vice President and Head of Development, Therapeutics and Oncology. "Selection for this program will enable enhanced communication with the U.S. FDA, resulting in acceleration of our development program as we prepare for pivotal study initiation for mRNA-3705 in 2024."

The START pilot program was initiated by the U.S. FDA in September 2023 to accelerate the development of novel treatments addressing unmet medical needs in rare diseases, with an initial selection of up to seven novel treatments, three by the Center for Drug Evaluation and Research (CDER) and four by the Center for Biologics Evaluation and Research (CBER). The milestone-driven initiative is intended to help the progression to pivotal clinical studies or pre-BLA/NDA meeting stages by enhancing communications between manufacturers and the U.S. FDA. Selected manufacturers will benefit from rapid, ad-hoc U.S. FDA interactions to support clinical development, such as study design, patient population, and statistical methods, beyond standard formal meetings. The program is designed to generate high-quality, reliable data to support marketing approvals, ensuring promising treatments advance efficiently through regulatory milestones.

MMA is a rare, life-threatening, inherited metabolic disorder that is most commonly (approximately 60% of cases) caused by a deficiency in the mitochondrial enzyme MUT. This deficiency can lead to metabolic crises due to a toxic buildup of acids in the body, progressing into multi-organ disease. As a result, MMA is associated with significant mortality and morbidity, and there are no approved therapies. Standard of care includes dietary and palliative measures. Currently, liver or combined liver and kidney transplants are the only effective treatments.

mRNA-3705 is being investigated in a Phase 1/2 study, called the "Landmark study," an adaptive, open-label study designed to evaluate the safety and tolerability of the investigational therapeutic administered via intravenous infusion in patients one year and older with isolated MMA due to methylmalonyl-CoA mutase (hMUT) deficiency.