Early trial results reported for epigenome editing therapy in rare muscular dystrophy

An experimental epigenome editing therapy has shown a favourable safety profile and increased lean muscle mass in patients with a rare muscular dystrophy in an early-stage trial.

Epicrispr Biotechnologies, the developer of EPI-321, reported interim results from the first three participants enrolled in its ongoing Phase 1 trial of the therapy for facioscapulohumeral muscular dystrophy (FSHD). After six months of follow-up, the company reported gains in lean muscle mass averaging 0.8 pounds, ranging from 0.5 to 1.3 pounds across the three patients. Some individual muscles increased in volume by up to 15 percent. The findings have been announced by the company but have not yet been published in a peer-reviewed journal.

'These results represent a major scientific breakthrough for both the FSHD community and the field of epigenetic medicine,' said Dr Amber Salzman, chief executive officer of 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.'

EPI-321 uses an adeno-associated virus vector to deliver an epigenome editing system designed to increase DNA methylation at the DUX4 gene, reducing its activity without altering the underlying DNA sequence. Abnormal activation of DUX4 is the primary genetic driver of FSHD, a form of muscular dystrophy that mainly affects the muscles of the face, shoulders and upper arms.

By May 2026, nine patients had been treated with a single dose of EPI-321. The first six patients were given a lower dose of 20 trillion vector genomes per kilogram of body weight (vg/kg) and the following three with a higher dose of 40 trillion vg/kg. So far, there have been no serious side-effects reported for either dose.

Enrolment and dose escalation in the first part of the trial, which is taking place across sites in the USA, Australia and New Zealand, have now been completed. Epicrispr said updated clinical results are expected to be presented at the World Muscle Society Annual Congress in September 2026, while the primary completion of the trial is anticipated in mid-2027.

'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 Professor Russell Butterfield, principal study investigator at the University of Utah.

Currently, there are no approved treatments for FSHD, and Roche has recently discontinued development of an investigational therapy for the condition.

'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', concluded Professor Butterfield.