Sanofi AAV gene therapy gets fast track tag in myotonic dystrophy

The U.S. FDA has granted fast track designation to Sanofi's one-time AAV gene therapy, SAR446268, for the treatment of non-congenital DM1 myotonic dystrophy type 1 (DM1).

DM1 is a rare, genetic disorder that causes progressive muscle weakness and wasting, with no currently approved medicines. SAR446268 is the only investigational therapy in clinical development for this disease.

SAR446268 employs a vectorized RNA interference (RNAi) approach to silence DMPK expression through a single administration. By reducing DMPK transcripts, the gene therapy aims to eliminate the abnormal and toxic RNA foci responsible for splicing defects in muscle tissue, restoring normal splicing and improving muscular function. The approach has the potential to address key symptoms of the disease, including progressive muscle weakness, difficulty relaxing muscles (myotonia), and effects on multiple body systems including heart, lungs, and endocrine functions.

The therapy is currently under investigation in a first-in-human, phase 1-2 study to evaluate the safety, tolerability, and efficacy, with the first patient planned for enrolment in late 2025. Sanofi has already been granted orphan designations for SAR446268 in both the U.S. (July 2024) and EU (October 2024).