Moderna's MMA candidate nabs spot in FDA pilot for rare disease drugs

Moderna’s methylmalonic acidemia candidate, mRNA-3705, will be developed under the FDA’s START pilot program for rare disease, the company announced June 6.

It joins therapies from Denali Therapeutics, Neurogene, Grace Sciences and Larimar Therapeutics in the initiative, which aims to do for rare disease drugs what Operation Warp Speed did for the COVID-19 vaccines.

Methylmalonic acidemia, or MMA, is a genetic liver condition that in most cases is caused by a deficiency in an enzyme called MUT, which processes fatty acids. Without it, the acids build up and damage organs. The disease is usually diagnosed within the first few months of life, and there are currently no treatments.

MRNA-3705 is an mRNA-based drug that encodes MUT, thereby restoring acid metabolism. It has orphan-drug, fast-track and rare pediatric disease designations from the FDA and is currently being tested in a 63-subject, phase 1/2 clinical trial

Under START, mRNA-2705 will get extra attention from FDA officials, who will guide Moderna through product development issues like designing studies, choosing control groups and selecting the right patient population. The effort is being carried out by the agency’s Center for Biologics Evaluation and Research and the Center for Drug Evaluation and Research, which is selecting six participants total for the first iteration of the program, according to a September 2023 announcement from the FDA. 

“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,” Kyle Holen, M.D., senior vice president and head of development in the therapeutics and oncology unit at Moderna, said in a press release. “Selection for this program will…[result] in acceleration of our development program as we prepare for pivotal study initiation for mRNA-3705 in 2024.”

Moderna's other rare disease programs include drugs for propionic acidemia, glycogen storage disorder type 1a, ornithine transcarbamylase deficiency, phenylketonuria, Crigler-Najjar syndrome type 1 and cystic fibrosis.

Also picked for the START program is Calico Life Sciences' eIF2B activator fosigotifator, which is under development for Vanishing White Matter disease. The condition is an ultra-rare disease of the brain's white matter caused by variations in an essential enzyme in the cells called eIF2B. This causes a reduction in enzymatic activity that can lead to chronic activation of the integrated stress response.  This causes the white matter to degenerate, causing symptoms such as impaired muscle movement, cognitive decline and seizures. Patients have a shortened life span. 

Fosigotifator is being developed in a partnership between Calico and AbbVie through an agreement signed in 2014.