Interim Phase 1/2 Results for Moderna's mRNA-3927 Therapy in Propionic Acidemia Patients

Moderna, a prominent biotechnology company, has reported interim findings from a clinical trial of mRNA-3927, an experimental mRNA therapy for propionic acidemia (PA), in a publication by Nature. PA is a rare genetic disorder characterized by an inability to metabolize certain proteins and fats due to enzyme deficiency, leading to a buildup of harmful substances in the body that can cause severe health issues.

Kyle Holen, Moderna's Senior Vice President for Development, Therapeutics and Oncology, expressed enthusiasm over the clinical data, highlighting the significance of mRNA-3927 as a potential intracellular protein replacement therapy. The study, which is ongoing, is designed to evaluate the safety and pharmacological aspects of mRNA-3927 in individuals over the age of one with genetically confirmed PA. The data from this study was initially presented at the 2023 American Society of Gene & Cell Therapy (ASGCT) Annual Meeting.

As of May 31, 2023, 16 participants received mRNA-3927 treatment across different cohorts. Of these, 12 completed the study and continued into an open-label extension. Over 340 doses were administered, amounting to more than 15 person-years of treatment. The therapy has shown good tolerability with no dose-limiting toxicities observed. While adverse events were reported, most serious adverse events were linked to PA itself rather than the treatment. Notably, there was a 70% reduction in the risk of metabolic decompensation events during the treatment period, and no such events were reported with higher doses of mRNA-3927.

The study is now enrolling additional participants to further assess the therapy's efficacy, safety, and pharmacodynamic activity. PA is a serious condition with significant morbidity and mortality, affecting approximately one in every 100,000 to 150,000 individuals globally. It is caused by mutations in genes responsible for an enzyme crucial for metabolizing certain substances, leading to the accumulation of toxic metabolites and recurrent, life-threatening complications.

mRNA-3927 is an innovative therapy administered intravenously, encapsulated in lipid nanoparticles, designed to encode for proteins that restore the activity of the deficient enzyme in the liver. Moderna, known for its pioneering work in mRNA technology, is at the forefront of developing new treatments and vaccines for a range of diseases, including one of the first effective COVID-19 vaccines.

The company's mRNA platform is a cornerstone of its efforts to develop therapeutics and vaccines for various diseases, with a commitment to improving human health responsibly.