Moderna, a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, reported on interim data from the Phase 1/2 trial of mRNA-3927, an investigational mRNA therapy for propionic acidemia (PA), presented at the 2023 American Society of Gene + Cell Therapy (ASGCT) Annual Meeting.

The ongoing global Phase 1/2 clinical trial (ClinicalTrials.gov Identifier: NCT04159103) is a multicenter, open-label study designed to assess the safety, pharmacodynamics, and pharmacokinetics of mRNA-3927 in participants aged 1 year and older with genetically confirmed PA. The trial utilized a dose-escalation approach to evaluate the intravenous administration of mRNA-3927.The initial dosing regimen was 0.3 mg/kg administered intravenously every three weeks; subsequent doses were administered every two weeks. Participants who complete the dose optimization trial (10 doses) are eligible to continue treatment in an open-label extension study (NCT05130437). The primary outcomes of the trial are safety and tolerability, while secondary and exploratory outcomes include pharmacology, evaluation of potential plasma biomarkers, and the frequency and duration of metabolic decompensation events (MDEs). mRNA-3927 has been well-tolerated at the doses administered, with encouraging early signs of dose-dependent pharmacology and potential clinical benefit.

To date, a total of 16 participants have received doses of mRNA-3927 across five dose cohorts. Of these, 11 participants completed the study and enrolled in the open-label extension study, and five participants were treated with mRNA-3927 for over one year. Following treatment initiation with mRNA-3927, most participants who had reported MDEs in the 12 months prior to dosing had either a lower incidence or no MDEs post-treatment.

In total, more than 280 doses of mRNA-3927 were administered across both studies, which is more than 13 patient-years' treatment experience. No dose-limiting toxicities or study discontinuations due to drug-related TEAEs have occurred. Fifteen participants reported TEAEs, while nine participants experienced drug-related TEAEs. Serious adverse events (SAEs) were reported in eight participants. Most SAEs were related to PA and unrelated to mRNA-3927. Six participants had mild infusion-related (IRR) TEAEs; however, most events occurred at the first doses.

"We continue to observe encouraging results with mRNA-3927 as we enter the dose-expansion phase, where we will further assess safety, efficacy, and determine the recommended dose for future clinical studies. This is the first clinical trial reporting results of an mRNA therapeutic for intracellular protein replacement, and we currently have more than 13 patient-years of experience to date," said Kyle Holen, M.D., Moderna's Senior Vice President and Head of Development, Therapeutics and Oncology. "We express our immense gratitude to the patients, families, and researchers who have contributed to our research efforts, and we look forward to continuing our efforts to explore the therapeutic potential of our mRNA platform for propionic acidemia and other rare diseases."