The early clinical evidence shows that mRNA-3927 can treat PA, a rare inherited metabolic disorder affecting one in every 100K – 150K individuals worldwide, by replacing intracellular proteins.
In the global, open-label study, children with PA received multiple doses of a lipid nanoparticle-encapsulated dual mRNA therapy.
Citing data from 16 trial participants who received mRNA-3927 doses across five dose cohorts, the biotech giant said the study drug was generally well-tolerated with no dose-limiting toxicities or study discontinuations.
According to Moderna, 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).
The company said patients who reported MDEs 12 months before dosing indicated a lower incidence or no events of MDE after receiving mRNA-3927.
However, 15 subjects reported treatment-emergent adverse events, and nine had drug-related TEAEs. In addition, eight patients developed severe adverse events, most of which were linked to PA and unrelated to mRNA-3927.
Moderna has now administered more than 280 doses of mRNA-3927, with five patients taking the therapy for more than one year, and is moving forward with the program.
“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,” said Kyle Holen, senior vice president and head of development, therapeutics and oncology at Moderna.
“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.
“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.”