On the 19th (local time), Moderna announced the interim results of phase 1/2 clinical trials of its propionic acidemia (PA) mRNA treatment candidate mRNA-3927 to the ‘2023 American Society of Gene + Cell Therapy’ (ASGCT) Annual Meeting)) ‘.
The ongoing global phase 1/2 clinical trial is an open-label, multicenter, dose-optimized study to evaluate the safety and pharmacology and pharmacokinetics of mRNA-3927 in participants 1 year of age and older with propionic acidemia after to confirm genetically (ClinicalTrials.gov Identifier: NCT04159103).
According to the company, the study uses a dose-escalation approach to evaluate intravenous administration of mRNA-3927. The initial dosing regimen was 0.3 mg/kg administered intravenously every 3 weeks, with subsequent doses administered every 2 weeks. Participants who complete the dose optimization trial (10 doses) are eligible to continue treatment in the open-label study (NCT05130437). The primary endpoints are safety and tolerability, secondary and exploratory endpoints include pharmacology, evaluation of potential plasma biomarkers, frequency and duration of metabolic decompensation events (MDE).
To date, a total of 16 patients have received mRNA-3927 in five dose cohorts. Of the 15 participants, 11 completed the study and enrolled in the open-label extension study, and 5 were treated with mRNA-3927 for one year or more. Most of the participants who reported metabolic decompensation (MDE) in the 12 months before mRNA-3927 treatment had no or low incidence of metabolic decompensation after mRNA-3927 treatment.
A total of more than 280 doses were administered in both studies, representing more than 13 patient years of patient administration. There were no study terminations due to dose-limiting toxicities or treatment-related adverse events. Treatment-related adverse reactions were reported in 15 participants and drug-related adverse reactions were reported in 9 participants. Serious adverse reactions were reported in 8 participants, but the majority were related to propionic acidemia and not to mRNA-3927. Six participants reported mild infusion-related adverse reactions, but most cases occurred with the first dose.
Kyle Hollen, Senior Vice President, General Manager, Therapeutics and Oncology, Moderna, said, “We continue to see encouraging results for mRNA-3927 as we enter a dose expansion phase that will further evaluate safety and efficacy and determine recommended doses for future clinical. studies.” This study is the first clinical result of mRNA treatment for intracellular protein replacement, and we have been able to obtain more than 13 patient years so far. Patients who contributed to this result and we greatly appreciate the family and the research team and look forward to continued efforts to explore the therapeutic potential of the mRNA platform for propionic acidemia and other rare diseases.”
