Moderna Therapeutics announced the U.S. Food and Drug Administration (FDA) has completed its review of the Investigational New Drug (IND) application for mRNA-3927, its investigational mRNA therapeutic for propionic acidemia (PA), a rare metabolic disease. With the IND approval, mRNA-3927 can now proceed to the clinic.
Moderna plans to initiate an open-label, multi-center, dose-escalation Phase 1/2 study of multiple ascending doses of mRNA-3927 in primarily pediatric patients with PA in the United States and Europe. The objectives of this study are to evaluate the safety and tolerability of mRNA-3927 administered via IV infusion, characterize the pharmacokinetic profile of mRNA-3927 and assess the pharmacodynamic response as assessed by changes in plasma biomarkers.
mRNA-3927 has been granted Orphan Drug and Rare Pediatric Disease designations from the FDA and Orphan Designation by the European Medicines Agency (EMA).
About Propionic Acidemia
PA is a rare, life-threatening, inherited metabolic disorder that is the result of a deficiency in PCC that is an enzyme critical for metabolism. This deficiency can lead to a toxic buildup of acids in the body. Symptoms of PA typically become apparent during infancy and may include weak muscle tone, poor feeding, vomiting and lack of energy. More severe health problems can also occur, including heart abnormalities, seizures, and coma.
The only effective treatment for severely affected individuals is a liver transplant, which replaces the deficient PCC enzyme. Currently, there are no approved therapies to treat the underlying cause of PA, including no enzyme replacement therapy, due to the complexity of the PCC enzyme that requires mitochondrial localization.
mRNA-3927 is designed to instruct the body to restore the missing or dysfunctional proteins that cause PA. mRNA-3927 contains two mRNAs that encode for the alpha and beta subunits of the mitochondrial enzyme propionyl-CoA carboxylase (PCC), encapsulated within Moderna’s proprietary lipid nanoparticle (LNP). mRNA-3927 is intended to treat patients with PA regardless of whether they are missing the alpha or beta subunits.