CAMBRIDGE, Mass. — Sarepta Therapeutics said it has reported initial clinical data from two investigational siRNA programs targeting rare neuromuscular diseases, including facioscapulohumeral muscular dystrophy type 1 and myotonic dystrophy type 1.
The early findings come from Phase 1/2 ascending dose studies evaluating SRP-1001 for FSHD1 and SRP-1003 for DM1. According to the company, the results showed dose-dependent muscle exposure, early biomarker activity, and favorable tolerability profiles.
Sarepta said the therapies achieved high concentrations in muscle tissue without dose-limiting toxicity. Most adverse events observed in the studies were mild to moderate and were not dose dependent.
The company also reported proof-of-concept data indicating that a single dose of either therapy was able to reduce, or knock down, target proteins or messenger RNA linked to disease progression.
Both programs use an αvβ6 integrin-targeted delivery platform designed to improve how siRNA therapies reach muscle cells. RNA-based treatments have shown promise for genetic conditions such as FSHD1 and DM1, but their effectiveness has historically been limited by rapid degradation before reaching target tissues.
“We are pleased that these early clinical results showed high levels of siRNA delivery to muscle, with no saturation of muscle siRNA uptake or dose-limiting safety signals to date. We believe this supports the differentiated potential of this siRNA platform and strengthens our belief that this approach could meaningfully change the treatment landscape for patients with FSHD and DM1,” said Louise Rodino-Klapac, Ph.D., President, Research & Development and Technical Operations. “These preliminary clinical data show consistent dose-dependent increases in plasma and muscle drug exposures across clinical and nonclinical studies and suggest that the αvβ6 integrin-targeting ligand mediates robust siRNA muscle delivery, which we hypothesize will ultimately enable higher dosing and translate into clinical efficacy for patients with FSHD1 and DM1.”
The investigational therapies are designed with optimized siRNA chemistry and a proprietary targeting ligand intended to enhance cellular uptake and muscle penetration, with the goal of overcoming delivery and safety challenges seen in earlier RNA-based approaches.
