Merck & Co. revealed results from a mid-stage clinical trial showing its GLP-1 and glucagon receptor co-agonist efinopegdutide resolved cases of metabolic dysfunction-associated steatohepatitis (MASH) compared with placebo without worsening liver fibrosis.
In the phase 2b trial called MK-6024-013, 386 patients with MASH and stage F2 or F3 fibrosis received one of three different doses of efinopegdutide or a placebo. the study met the primary endpoint of resolving MASH in 56% of patients at 4 mg, 63% at 7 mg and 61% at 10 mg at 52 weeks. The placebo arm notched 13% resolution of the liver disease, which is measured by a scoring system set down by the Non-alcoholic Steatohepatitis Clinical Research Network.
The subcutaneously injected efinopegdutide co-activates the two receptors GLP-1 and glucagon to resolve MASH, which if left untreated can lead to fibrosis, cirrhosis and liver failure, and it’s estimated that around 5% of the world live with the disease, according to a release from Merck.
The study showed meaningful improvements in fibrosis without worsening of MASH, resulting in 43%, 52% and 34% response rates at the three doses compared with 21% for placebo.
Merck also included a research arm in the newest study including patients who received Novo’s semaglutide at 2.4 mg, in which 53% achieved the MASH resolution endpoint without worsening of fibrosis. Novo’s Wegovy, which is a formulation of semaglutide, is the only GLP-1 approved for MASH, getting the FDA go-ahead last year.
In 2024, Merck showcased phase 2 data that demonstrated efinopegdutide outperformed Novo’s Ozempic in patients with MASH, at the time known as nonalcoholic fatty liver disease (NAFLD). At the time, Merck posted a 72.7% reduction in liver fat content over the course of eight months compared to 42.3% for Ozempic.
Merck’s journey with efinopegdutide began in 2020 when the pharma giant licensed the drug candidate from Hanmi Pharmaceutical, which had previously picked it up from Johnson & Johnson’s pipeline discard pile. Merck paid $10 million for the rights, while Hanmi had paid J&J $105 million in 2015.
With efinopegdutide, Merck hopes to enter the widely popular realm of GLP-1 drugs that have taken the world by storm, including Novo’s Ozempic and Wegovy, as well as market leader Eli Lilly’s Mounjaro and Zepbound. But while these blockbusters have climbed on the basis of their weight-loss clout, a MASH indication could help Merck’s asset stand out.
Safety was similar to that of semaglutide, the company pointed out, with nausea, diarrhea and vomiting resulting in single- to low-double-digit discontinuation over the course of the year-long study.