Cambridge, Massachusetts-based Prime Medicine (Nasdaq: PRME) dosed the first patient in a global Phase I/II trial of PM577a, an investigational in vivo prime-editing therapy for Wilson disease caused by the H1069Q mutation in the ATP7B gene.
The open-label study (NCT07748403) will evaluate ascending doses of PM577a in adults and adolescents carrying at least one p.H1069Q allele. Initial enrollment will focus on clinically stable adults receiving standard-of-care treatment, with efficacy assessments including copper efflux by 64Cu PET, serum ceruloplasmin, non-ceruloplasmin-bound copper, and 24-hour urinary copper excretion. Prime expects initial clinical data in 2027.
PM577a is designed as a one-time intravenous therapy that uses a lipid nanoparticle to deliver prime-editing machinery to hepatocytes and correct the H1069Q mutation. The mutation is the most prevalent Wilson disease-causing allele in North America and Europe. The US FDA has granted Rare Pediatric Disease designation to the PM577 program.
Prime Editing was developed in the laboratory of Prime Medicine co-founder David Liu at the Broad Institute of MIT and Harvard. The technology uses a Cas-derived nickase fused to a reverse transcriptase to introduce precise DNA sequence changes without relying on a conventional double-strand DNA break or homology-directed repair, an approach that may be advantageous in largely nondividing tissues such as the adult liver.