Merck's efinopegdutide meets Phase 2b MASH endpoint

Merck said on November 9, 2026, that once-weekly injectable efinopegdutide (MK-6024), an investigational GLP-1/glucagon receptor co-agonist, met the primary endpoint of a Phase 2b trial in adults with metabolic dysfunction-associated steatohepatitis, or MASH, and stage F2 or F3 fibrosis. The results were presented at The Liver Meeting in Denver and published the same day in The Lancet. Merck’s release is time-stamped 1:05 p.m. ET.

Efinopegdutide is a subcutaneous injection, not a pill. Merck said it is being developed under an exclusive license from Hanmi Pharmaceutical and has received Fast Track designation from the U.S. Food and Drug Administration for the treatment of MASH. It is not an approved MASH therapy.

The trial

MK-6024-013 (NCT05877547) is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled study of once-weekly subcutaneous efinopegdutide after 52 weeks of treatment. ClinicalTrials.gov lists the study as completed, with actual enrollment of 381. Merck said the trial enrolled 386 adults with biopsy-confirmed MASH and stage F2 or F3 fibrosis, and that 381 were randomized and received at least one dose: efinopegdutide “4 mg” (n=77), “7 mg” (n=77), or “10 mg” (n=79); placebo (n=79); and open-label semaglutide “2.4 mg” (n=69). Merck said 92% (349 of 381) completed the study.

The primary efficacy endpoint was the share of participants with MASH resolution without worsening of fibrosis at 52 weeks, assessed with the NASH Clinical Research Network scoring system by blinded independent central review.

MASH resolution and fibrosis

Merck said the study met that primary endpoint. The shares with MASH resolution and no fibrosis worsening were 56% on “4 mg”, 63% on “7 mg”, and 61% on “10 mg”, each with p under 0.0001, versus 13% on placebo.

On a key secondary histologic endpoint, improvement of at least one fibrosis stage with no worsening of steatohepatitis, Merck reported response rates of 43%, 52%, and 34% across the “4 mg”, “7 mg”, and “10 mg” groups, compared with 21% for placebo. Merck described those results as “meaningful improvements” and did not print p-values for the fibrosis endpoint in its release. HCPLive, reporting the presentation by Professor Jörn M. Schattenberg, said the differences versus placebo were statistically significant for “4 mg” (21.7 percentage points; P=.004) and “7 mg” (30.4 percentage points; 95% CI, 15.4 to 44.3; P under .001), but not for “10 mg” (P=.072). That qualification is from the meeting report, not from Merck’s release.

The trial also included an open-label semaglutide “2.4 mg” arm as what Merck called an “active reference arm.” HCPLive reported that 53% of participants in that arm met the primary MASH-resolution endpoint and that 25% had at least a one-stage fibrosis improvement. Those semaglutide figures are from HCPLive, not from the Merck release. HCPLive also reported that Schattenberg cautioned the semaglutide arm “was not a direct comparison for the primary endpoint.” It is not a blinded head-to-head test.

Safety

On gastrointestinal events, Merck reported nausea in 29% of the “4 mg” group, 39% of the “7 mg” group, and 44% of the “10 mg” group; the open-label semaglutide rate was 39%, and the placebo rate was 11%. Diarrhea was listed at 29%, 26%, and 22% on those three efinopegdutide doses, 22% on open-label semaglutide, and 20% on placebo. Vomiting was listed at 20%, 8%, and 28%, compared with 15% and 3%. People who stopped treatment because of adverse events accounted for 3%, 4%, and 11% of the efinopegdutide arms, and 1% of both the open-label semaglutide and placebo arms. HCPLive said investigators concluded the “7 mg” dose had the most favorable benefit-risk profile.

Eliav Barr, Merck’s chief medical officer, said the company is “highly encouraged by these results” and that the drug “has the potential to provide clinically meaningful responses for MASH resolution and fibrosis regression.” That is a company assessment, not a regulatory finding.

HCPLive also noted that semaglutide “2.4 mg” has accelerated approval in the United States for noncirrhotic MASH with F2-F3 fibrosis, based on the Phase 3 ESSENCE trial.

What is not known

• The Lancet tables. Merck said the results were published in The Lancet but did not cite a DOI in its release, and the fibrosis p-values used here come from HCPLive’s account of the presentation, not from a retrieved journal abstract.
• How the “10 mg” fibrosis result should be read. The primary endpoint was met at all three doses. The key secondary fibrosis rate at “10 mg” was higher than placebo in Merck’s release, but HCPLive reported that comparison was not statistically significant.
• The semaglutide arm is not a comparative trial. Open-label semaglutide figures should not be treated as a formal head-to-head result.
• Later-stage development. The Merck release does not announce a Phase 3 start in this population. HCPLive said Merck is evaluating compensated cirrhosis in a separate Phase 2 trial (NCT06465186). Efinopegdutide remains investigational.