Moderna announces publication of Phase 1/2 interim data on mRNA-3927

Moderna announced that interim data for a first-in-human, phase 1/2, open-label, dose optimization study and extension study, evaluating the safety and efficacy of mRNA-3927, an investigational mRNA therapy for propionic acidemia, has been published in Nature. “We are excited to share the first published clinical data utilizing an mRNA therapy for intracellular protein replacement,” said Kyle Holen, M.D., Moderna’s Senior Vice President and Head of Development, Therapeutics and Oncology. “PA is a rare, inherited metabolic disorder that results from the body’s inability to process certain parts of proteins and lipids due to a specific enzyme deficiency. For people with PA, harmful amounts of toxic metabolites can build up in the body and lead to metabolic decompensation events and multisystemic complications. These interim data indicate early signs of potential clinical benefit with mRNA-3927, and importantly also demonstrate that mRNA-3927 has infrequent treatment-limiting side effects. I’m particularly proud of these results given that there are currently no therapeutic treatments approved for patients with this disease.” The ongoing global Phase 1/2 clinical trial is a multicenter, open-label study designed to assess the safety, pharmacodynamics, and pharmacokinetics of mRNA-3927 in participants aged one year and older with genetically confirmed PA. Data from the study was previously presented at the 2023 American Society of Gene & Cell Therapy Annual Meeting. As of the latest data cut, 16 participants received investigational therapy mRNA-3927 across five cohorts as part of the dose optimization and extension studies. Of these, 12 participants completed the study and enrolled in the open-label extension study. Over 340 intravenous doses were administered, accounting for over 15 person-years of treatment. To date, mRNA-3927 has been well tolerated in participants at the doses administered, with no dose-limiting toxicities observed. Fifteen participants reported treatment-emergent adverse events while nine participants experienced drug-related TEAEs. Serious adverse events were reported in eight participants. Most SAEs were related to PA and unrelated to mRNA-3927. Five participants had mild infusion-related TEAEs; however, most events occurred at the first doses. A reduction in the number of MDEs was observed. The relative risk for MDEs was reduced by 70% during the treatment period of the dose optimization study. No MDEs were observed with higher doses of mRNA-3927. Additional participants are now being enrolled into the study as part of a dose expansion phase to allow for further characterization of the efficacy, safety, and pharmacodynamic activity of mRNA-3927.