Merck reports positive Phase 2b efinopegdutide data in MASH with F2–F3 fibrosis
- MK-6024-013 randomized 381 participants with biopsy-confirmed MASH and F2–F3 fibrosis (386 enrolled; 92% completed).
- MASH resolution without worsening fibrosis at 52 weeks: efinopegdutide 4 mg 56% (p<0.0001), 7 mg 63% (p<0.0001), 10 mg 61% (p<0.0001) vs placebo 13%.
- Fibrosis improvement ≥1 stage without worsening steatohepatitis at Week 52: 43% (4 mg), 52% (7 mg), 34% (10 mg) vs 21% placebo.
- Safety signals: nausea 29–44% across efinopegdutide doses vs 39% semaglutide and 11% placebo; discontinuations for adverse events 3–11% vs 1% for semaglutide and placebo.
Trial and presentation
The Phase 2b MK-6024-013 trial randomized adults with biopsy-confirmed metabolic dysfunction‑associated steatohepatitis (MASH) and stage F2–F3 fibrosis to once-weekly subcutaneous efinopegdutide (4, 7 or 10 mg), placebo or an open-label semaglutide 2.4 mg reference arm. Of 386 enrolled, 381 received at least one dose and 92% completed 52 weeks. Results were presented at The Liver Meeting and published in The Lancet.
Efficacy
The study met its primary endpoint: MASH resolution without worsening fibrosis at Week 52. Response rates were 56% (4 mg), 63% (7 mg) and 61% (10 mg) versus 13% for placebo (all p<0.0001). A key secondary endpoint—fibrosis improvement of ≥1 stage without worsening steatohepatitis—occurred in 43%, 52% and 34% of the 4 mg, 7 mg and 10 mg groups, respectively, versus 21% for placebo.
Safety
Overall safety was described as generally consistent with semaglutide. Reported adverse-event rates included nausea (29%, 39%, 44% for efinopegdutide 4/7/10 mg; 39% semaglutide; 11% placebo), diarrhea (29%, 26%, 22%; 22%; 20%) and vomiting (20%, 8%, 28%; 15%; 3%). Discontinuations due to adverse events were 3%, 4% and 11% for efinopegdutide doses versus 1% for semaglutide and placebo.
Candidate profile and development
Efinopegdutide (MK-6024) is a once-weekly GLP‑1/glucagon receptor co-agonist designed to combine GLP‑1–mediated metabolic effects with glucagon-driven energy expenditure, lipid metabolism and hepatic anti‑steatotic activity. It has received FDA Fast Track designation for MASH and is being developed by Merck under an exclusive license with Hanmi Pharmaceutical.
Source: Merck