Sarepta Advances siRNA Pipeline with Early FSHD and DM1 Trial Data

Sarepta Therapeutics has reported the first clinical results from two investigational small interfering RNA (siRNA) programs targeting rare neuromuscular diseases, demonstrating early signs of effective muscle delivery, biomarker activity, and favorable tolerability in Phase 1/2 studies.

The data come from ascending-dose Phase 1/2 trials evaluating SRP-1001 (NCT06131983) for Facioscapulohumeral Muscular Dystrophy Type 1 (FSHD1) and SRP-1003 (NCT06138743) for Myotonic Dystrophy Type 1 (DM1). Early findings showed dose-dependent increases in siRNA exposure in muscle tissue along with preliminary biomarker effects, supporting the company’s αvβ6 integrin-targeted delivery platform designed to improve uptake of RNA therapies in muscle cells.

In both studies, a single dose of the investigational therapies demonstrated proof-of-concept activity, showing reduction of the disease-associated target protein or mRNA. Safety findings were generally favorable, with most adverse events reported as mild to moderate and not dose-dependent.

Sarepta’s approach combines optimized siRNA chemistry with a proprietary ligand that targets the αvβ6 integrin receptor. This strategy aims to enhance delivery of siRNA molecules into muscle tissue, addressing a major challenge for RNA-based therapies where rapid degradation can limit drug exposure at the intended site of action.

According to Louise Rodino-Klapac, Ph.D., President of Research & Development and Technical Operations at Sarepta, the early clinical results showed high levels of siRNA delivery to muscle without evidence of saturation or dose-limiting safety signals. The company believes the targeted delivery platform could allow higher dosing and potentially translate into clinical benefit for patients with FSHD1 and DM1.

FSHD is a rare genetic disorder caused by abnormal activation of the DUX4 gene, leading to toxic protein production that damages muscle cells and results in progressive muscle weakness. Approximately 16,000 individuals in the United States are diagnosed with the disease, and there are currently no disease-modifying treatments available.

DM1 is the most common adult-onset muscular dystrophy and is caused by repeat expansions in the DMPK gene that produce toxic RNA affecting multiple organ systems including skeletal muscle, heart, and respiratory function. An estimated 40,000 individuals in the United States are living with the condition, which also lacks disease-modifying therapies.

SRP-1001 is designed to silence production of the DUX4 protein in skeletal muscle in patients with FSHD1, while SRP-1003 targets toxic DMPK mRNA in DM1. Both investigational therapies are being evaluated in randomized, placebo-controlled Phase 1/2 trials with single-ascending and multiple-ascending dose designs.

Sarepta is also advancing a broader pipeline of siRNA therapies for neurological and pulmonary diseases under an exclusive license agreement with Arrowhead Pharmaceuticals.

References

Sarepta Therapeutics. Sarepta announces first clinical data from siRNA pipeline targeting FSHD1 and DM1. 2026. Available from: https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-announces-first-clinical-data-sirna-pipeline-targeting

Study of ARO-DUX4 in Adult and Adolescent Patients with Facioscapulohumeral Muscular Dystrophy Type 1, ClinicalTrials.gov ID NCT06131983, https://clinicaltrials.gov/study/NCT06131983

Study of ARO-DM1 in Subjects with Type 1 Myotonic Dystrophy, ClinicalTrials.gov ID NCT06138743, https://clinicaltrials.gov/study/NCT06138743