San Francisco — Epicrispr Biotechnologies reported interim results from an ongoing Phase 1/2 clinical trial showing increased lean muscle volume in the first three evaluable patients with facioscapulohumeral muscular dystrophy treated with its experimental therapy EPI-321.
The clinical-stage biotechnology company said the findings represent the first reported clinical evidence of increased muscle volume following treatment in patients with facioscapulohumeral muscular dystrophy, or FSHD.
FSHD is a progressive neuromuscular disease that causes ongoing muscle degeneration and weakness. There are currently no approved treatments for the condition.
As of the May 12 data cutoff, nine patients had received EPI-321 across two dose groups. Six patients received a single intravenous infusion at the target dose of 2×10¹³ vector genomes per kilogram, while three received a dose of 4×10¹³ vector genomes per kilogram.
Epicrispr said EPI-321 demonstrated a positive safety profile, with no serious adverse events reported to date.
The first three evaluable patients in the target-dose group showed gains in lean muscle volume six months after treatment compared with baseline. The average increase was about 370 milliliters, equivalent to roughly 0.8 pounds of muscle mass.
Individual gains ranged from about 0.5 pounds to 1.3 pounds, while some muscles showed increases of as much as 15% in lean muscle volume, according to the company.
Epicrispr previously reported improvements in several strength and functional measures at three months in the same patients. The company said the muscle-volume findings contrasted with the progressive muscle loss historically observed in FSHD studies, including recent Phase 3 trials.
EPI-321 is designed to silence DUX4, the genetic driver of FSHD. The therapy uses Epicrispr’s Gene Expression Modulation System platform to regulate disease-causing gene expression without changing the underlying DNA sequence.
The single-dose investigational therapy is intended to provide long-lasting suppression of DUX4 activity and protect muscles from damage associated with the gene.
“These results represent a major scientific breakthrough for both the FSHD community and the field of epigenetic medicine,” said Amber Salzman, Ph.D., Chief Executive Officer, Epicrispr Biotechnologies. “For the first time, we are seeing clinical evidence that a therapy may suppress the genetic driver of FSHD and increase muscle volume. The alignment between imaging, biomarker, and functional data strengthens our confidence in the potential of EPI-321 to meaningfully alter the course of disease.”
The magnetic resonance imaging results were supported by reductions in a circulating cell-free DNA biomarker associated with DUX4 pathway activity. Epicrispr said the biomarker findings were consistent with the increases in muscle volume and favorable trends in strength and function.
“Patients with FSHD face a lifelong, progressive loss of muscle that can affect nearly every aspect of daily living, from walking and climbing stairs to maintaining independence,” said Russell Butterfield, M.D., Principal Study Investigator and Associate Professor in Pediatrics & Neurology, University of Utah. “Historically, we have had very limited ability to alter the course of the disease. Although these are early results and additional follow-up is needed, the observed changes in lean muscle volume are encouraging and suggest EPI-321 may be addressing the underlying drivers of disease in a way that could ultimately translate into meaningful benefit for patients.”
The MRI analyses were conducted with Springbok Analytics, which uses artificial intelligence to measure muscle volume and other biomarkers from whole-body MRI scans. The platform assessed changes across as many as 140 individual muscles.
“The consistency of the MRI findings across all evaluable patients was remarkable, particularly in a disease where muscle deterioration is expected over time,” said Silvia Blemker, Ph.D., Chief Scientific Officer, Springbok Analytics. “Our quantitative whole-body MRI and AI-powered muscle analysis, enabled objective assessment of changes in lean muscle volume across up to 140 individual muscles throughout the body. While these are early results, the data highlight the value of advanced imaging in capturing treatment-related changes that may not be apparent through traditional clinical assessments.”
The open-label Phase 1/2 study is evaluating the safety, tolerability, biological activity and preliminary efficacy of EPI-321 in adults with FSHD.
Epicrispr expects to present additional results at the World Muscle Society Annual Congress in September and complete the primary portion of the study in mid-2027.
