Moderna's MMA Drug Chosen for FDA Rare Disease Pilot

Moderna has announced the development of its methylmalonic acidemia (MMA) treatment candidate, mRNA-3705, under the U.S. FDA's START pilot program for rare diseases as of June 6. This initiative aims to accelerate the development of medications for rare conditions, similar to the rapid development efforts seen with COVID-19 vaccines under Operation Warp Speed. Other participants in the START program include Denali Therapeutics, Neurogene, Grace Sciences, and Larimar Therapeutics.

Methylmalonic acidemia is a genetic disorder primarily caused by a deficiency in an enzyme called MUT, which is crucial for processing fatty acids. The absence of this enzyme leads to the accumulation of harmful acids that can damage vital organs. Typically diagnosed within the first few months of life, MMA currently has no existing treatments.

Moderna's mRNA-3705 is an innovative mRNA-based drug designed to encode the MUT enzyme, thereby aiding in the proper metabolism of acids. This therapeutic candidate has already received orphan-drug, fast-track, and rare pediatric disease designations from the FDA. It is currently undergoing a phase 1/2 clinical trial involving 63 participants.

The START program provides mRNA-3705 with enhanced regulatory support from FDA officials, who will assist Moderna in navigating various aspects of product development. This includes guidance on study design, control group selection, and patient population targeting. The initiative is managed by the FDA’s Center for Biologics Evaluation and Research and the Center for Drug Evaluation and Research. According to a September 2023 announcement, the program will include six participants initially.

Dr. Kyle Holen, Senior Vice President and Head of Development in the Therapeutics and Oncology Unit at Moderna, emphasized the significance of this selection. He mentioned that it underscores the potential of Moderna’s mRNA platform beyond vaccines and its promise in addressing the unmet medical needs associated with MMA. Being part of the START program is expected to expedite the development process of mRNA-3705, with preparations underway for pivotal study initiation in 2024.

In addition to mRNA-3705, Moderna is also working on other treatments for rare diseases. These include therapies for propionic acidemia, glycogen storage disorder type 1a, ornithine transcarbamylase deficiency, phenylketonuria, Crigler-Najjar syndrome type 1, and cystic fibrosis.

Another participant selected for the START program is Calico Life Sciences, which is developing fosigotifator, an eIF2B activator, for Vanishing White Matter disease. This ultra-rare brain disorder results from variations in the eIF2B enzyme, leading to chronic activation of the integrated stress response and degeneration of the brain's white matter. Symptoms include impaired muscle movement, cognitive decline, and seizures, significantly shortening the patients' lifespan.

Fosigotifator is being developed through a collaboration between Calico and AbbVie, formalized in an agreement signed in 2014. This partnership aims to address this debilitating condition by enhancing enzymatic activity to mitigate the disease's progression.

Overall, the START program represents a significant step forward in the development and acceleration of treatments for rare diseases, providing much-needed hope for patients and their families. Moderna's involvement in the program highlights the potential of mRNA technology to address complex and previously untreatable genetic disorders.