Merck has reported positive Phase 2b results for its experimental MASH drug efinopegdutide, with up to 63% of patients achieving disease resolution without worsening of liver fibrosis after 52 weeks of treatment.

 

The findings offer fresh momentum in the search for effective treatments for metabolic dysfunction-associated steatohepatitis (MASH), a progressive liver disease that can lead to cirrhosis and liver failure.

 

In the Phase 2b MK-6024-013 trial, efinopegdutide met its primary endpoint, demonstrating statistically significant improvements across all three doses tested compared with placebo.

 

MASH resolution rates were 56% among patients receiving the 4 mg dose, 63% with the 7 mg dose and 61% with the 10 mg dose. This compared with just 13% in the placebo group. All three treatment groups achieved highly statistically significant results.

 

The investigational once-weekly injectable drug also demonstrated improvements in liver fibrosis, a critical measure of disease progression. The proportion of patients achieving at least a one-stage improvement in fibrosis without worsening of steatohepatitis was 43% with the 4 mg dose, 52% with 7 mg and 34% with 10 mg, compared with 21% for placebo.

 

“MASH poses a substantial risk of progression to cirrhosis and ultimately liver failure, underscoring the urgent need for new treatment options,” said Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. 

 

“We are highly encouraged by these results which add to the evidence that efinopegdutide, a distinct GLP-1/glucagon receptor co-agonist, has the potential to provide clinically meaningful responses for MASH resolution and fibrosis regression.”

 

Efinopegdutide is an investigational GLP-1/glucagon receptor co-agonist designed to combine the metabolic and appetite-regulating effects of GLP-1 activation with glucagon's potential to increase energy expenditure, improve lipid metabolism and reduce liver fat.

 

The Phase 2b study evaluated three once-weekly doses of efinopegdutide against placebo, with an open-label semaglutide 2.4 mg arm serving as an active reference.

 

The trial enrolled 386 adults with biopsy-confirmed MASH and moderate-to-advanced liver fibrosis. A total of 381 participants received at least one dose of study treatment, and 92% completed the 52-week study.

 

Commenting on the findings, Professor  Jӧrn  M. Schattenberg, Department of Internal Medicine II, Saarland University Medical Center, Homburg, Germany, said: "MASH is a chronic inflammatory liver disease, with limited treatment options. Achieving disease resolution establishes an important treatment goal."

 

"The improvements observed in fibrosis grading following efinopegdutide treatment in this study are notable and underscore its potential as a therapeutic option in patients with MASH and fibrosis."