Epicrispr Biotechnologies has used its gene silencing tech to boost muscle mass in three patients with facioscapulohumeral muscular dystrophy, a clinical first for the debilitating disease with no approved treatments.
In an ongoing phase 1/2 study, the Bay Area biotech has so far dosed nine patients across two dose cohorts. For three patients given the lower dose, the company’s epigenetic editor, EPI-321, lead to an average increase in lean muscle of about 0.8 pounds, Epicrispr announced today.
Each of the three patients had more lean muscle six months after the single IV infusion of EPI-321, according to the release, ranging from about 0.5 pounds more to 1.3 pounds.
“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,” Russell Butterfield, M.D., a pediatrician and neurologist at the University of Utah and principal investigator of the trial, said in the release.
Epicrispr, a Fierce 15 honoree in 2023, uses a viral vector to deliver an enzyme that adds methyl groups to a gene called Dux4. Methylation is used by cells to silence genes, and by suppressing Dux4 Epicrispr hopes to quiet the sporadic expression of the gene that causes FSHD.
Treatment led to no serious adverse events, the company said in today’s release.
“These results represent a major scientific breakthrough for both the FSHD community and the field of epigenetic medicine,” Epicrispr CEO Amber Salzman, Ph.D., said in the release. “For the first time, we are seeing clinical evidence that a therapy may suppress the genetic driver of FSHD and increase muscle volume.”
FSHD affects around 870,000 people around the globe, Epicrispr said, causing muscle wasting mostly in the face and upper body but sometimes spreading to other muscles too.
Other attempts to develop medicines for FSHD have struggled, most notably Sanofi’s licensed program from Fulcrum Therapeutics. That candidate, losmapimod, failed spectacularly in a phase 3 trial back in 2024.
Roche’s Genentech, too, recently scrapped a phase 2 FSHD trial of its anti-myostatin antibody emugrobart after the molecule “did not consistently deliver the hoped-for improvements in muscle growth and function.”
Others racing to become the first with an approved FSHD drug are Sarepta Therapeutics, with an siRNA candidate licensed from Arrowhead Pharmaceuticals, and Novartis, which acquired an RNA contender of its own through its $12 billion buy of Avidity Biosciences.
Novartis CEO Vas Narasimhan, M.D., has said that the Big Pharma wants to become “one of the leaders in neuromuscular diseases.”
When it comes to the competition, though, Epicrispr is clear on where it stands. No other drug candidate has ever shown the ability to boost muscle in patients with FSHD, the company said in its release. A 2025 study from the University of Rochester found that 19 men with FSHD treated with a combination of testosterone and growth hormone gained an average of 4.5 pounds of lean muscle.