FDA selects Moderna’s mRNA therapy for rare disease pilot program

The Food and Drug Administration (FDA) has recently filled the penultimate slot in its new rare disease accelerator program with an mRNA therapy developed by Moderna. This therapy, mRNA-3705, is one of twelve programs that signify Moderna's strategic expansion beyond its focus on infectious diseases. Currently, mRNA-3705 is undergoing a Phase I/II Landmark trial to treat methylmalonic acidemia (MMA), a metabolic disorder due to methylmalonic-CoA mutase deficiency in patients aged one year and older. MMA is a serious condition with no approved therapies, often necessitating liver or combined liver and kidney transplants due to its high mortality rate.

Kyle Holen, who leads Moderna's development for therapeutics and oncology, emphasized that mRNA-3705's selection in the FDA pilot underscores the potential of Moderna's mRNA technology beyond vaccines. He pointed out the promise this novel medicine holds for addressing the significant unmet medical needs associated with MMA. Holen also mentioned that Moderna intends to initiate a pivotal trial for mRNA-3705 within the year.

The candidate is the sixth experimental treatment announced for the FDA's Support for Clinical Trials Advancing Rare Disease Therapeutics (START) program. Launched in September of last year, START aims to expedite the development of mid- to late-stage drugs and biologics for rare diseases. Participants in this program receive frequent guidance and communication from FDA staff on various development issues, including study design and patient recruitment. The initiative is structured to ensure that promising treatments progress efficiently through regulatory milestones.

The START program's design entails splitting participating therapies between drugs and biologics. The FDA’s Center for Drug Evaluation and Research is responsible for selecting three products targeting rare neurodegenerative conditions. Meanwhile, the Center for Biologics Evaluation and Research (CBER) focuses on choosing four cell or gene therapies aimed at treating rare diseases that could lead to significant disability or death within the first ten years of life.

The roster of candidates, initially revealed at the end of May, includes several notable therapies. Larimar Therapeutics’ nomlabofusp is a protein replacement therapy designed for Friedreich’s ataxia. Grace Science’s GS-100 is an AAV9 gene therapy aimed at NGLY1 deficiency. Myrtelle’s rAAV-Olig001-ASPA is a gene therapy in development for Canavan disease. Denali Therapeutics’ DNL126 serves as an enzyme replacement therapy for MPS IIIA. Lastly, Neurogene’s NGN-401 is a gene therapy for Rett syndrome. An additional participant in the program has yet to be disclosed.

The inclusion of mRNA-3705 in the START program not only marks a significant milestone for Moderna but also highlights the broader potential of mRNA therapies in treating a range of rare diseases. This initiative by the FDA reflects a concerted effort to support the development of cutting-edge treatments that address critical and unmet medical needs. By providing ongoing support and regulatory guidance, the FDA aims to accelerate the availability of these promising therapies to patients who need them the most.