Gene Therapy Fast Tracked for Non-Congenital Myotonic Dystrophy Type 1

The Food and Drug Administration (FDA) has granted Fast Track designation to SAR446268 for the treatment of non-congenital (juvenile and adult onset) myotonic dystrophy type 1 (DM1).

DM1 is an inherited rare disorder caused by mutations in the DMPK gene, resulting in progressive muscle weakness, myotonia, and other systemic dysfunctions. SAR446268 is a one-time adeno-associated viral gene therapy that delivers a vectorized RNA interference to silence DMPK expression, thereby preventing splicing defects in muscle tissue. 

An open-label, single-arm, phase 1/2 study (ClinicalTrials.gov Identifier: NCT06844214) is currently underway to evaluate the safety, tolerability, and efficacy of SAR446268 in participants aged 10 to 50 years with non-congenital DM1. Patients were eligible to be included in the study if they had a genetic diagnosis of DM1 (cytosine-thymine-guanine repeat length ≥50 in 1 allele) and were able to walk independently for at least 10 meters at screening, with or without orthoses or ankle braces. 

The study will consist of a dose escalation phase, in which single ascending doses of intravenous SAR446268 will be investigated in multiple cohorts, as well as a dose expansion phase. For the dose expansion phase, the primary endpoint is the proportion of participants with at least 40% DMPK mRNA knockdown in muscle biopsy at weeks 12 and 52 following treatment administration. 

SAR446268 was previously granted Orphan Drug designation. There are currently no approved therapies for DM1.

This article originally appeared on MPR