South San Francisco-based Epicrispr Biotechnologies reported six-month data from its first-in-human Phase I/II study of EPI-321 in facioscapulohumeral muscular dystrophy (FSHD), focused on the first six patients to reach that follow-up point. The patients showed increases in lean muscle volume and muscle strength, with the findings presented at the World Muscle Society annual congress.
EPI-321 is an adeno-associated virus (AAV)-delivered epigenetic gene therapy directed to skeletal muscle that re-methylates the D4Z4 region of the genome, suppressing expression of DUX4, the aberrantly expressed gene implicated in FSHD pathology.
FSHD affects more than an estimated 1 million people worldwide and has no approved disease-modifying therapies, according to Epicrispr Biotechnologies. The company's fully enrolled, open-label Phase I/II study is evaluating the safety, tolerability, biological activity, and preliminary efficacy of a single intravenous infusion of EPI-321 at two dose levels in adults with FSHD.
At six months, whole-body MRI showed a 3.0% increase in upper-body lean muscle volume versus a predicted 3.5% decline in a matched digital twin from natural history data. Upper-body strength improved 4.1% on quantitative muscle testing compared with a 0.3% decline in a matched external comparator from the ReSolve FSHD natural history study. The company described the safety profile as manageable, with no EPI-321-related serious adverse events. One participant experienced severe ALT and AST elevations considered related to AAV that responded to high-dose methylprednisolone without clinical sequelae