To break into the lucrative weight loss market, Merck will focus on the development of next-generation anti-obesity medications that offer additional cardiometabolic benefits beyond simple body weight reduction, company executives said on Tuesday.

During the 45th Annual Goldman Sachs Healthcare Conference, Merck CEO Robert Davis said that the pharma is focusing its R&D efforts more on small molecule oral drugs rather than injectables. “We’re very much focused on the second- and third-generation opportunities,” Davis said, adding that it is looking to advance GLP-1-targeting candidates that target other conditions on top of eliciting weight loss.

“I think everything is couched in terms of obesity first, and then we think about some of these outcomes kind of supporting the reimbursement within the broader obesity space,” Davis said.

Merck’s entry to the GLP-1 market is efinopegdutide, which is an investigational peptide therapeutic that also activates the glucagon receptor. While activating both the GLP-1 and glucagon pathways is a well-known mechanism of action for its weight loss and anti-diabetic effects, Merck is instead trialing efinopegdutide primarily as a treatment for metabolic dysfunction-associated steatohepatitis (MASH).

The exact mechanism of efinopegdutide for treating MASH is not yet completely understood, but it might reduce liver damage, steatosis and inflammation.

Merck exclusively licensed efinopegdutide from Hanmi Pharmaceutical in 2020 for $10 million upfront and the promise of up to $860 million in milestones. In June 2023, the FDA granted the GLP-1/glucagon receptor dual agonist its Fast Track designation for MASH.

In addition to MASH, Merck is also developing efinopegdutide for non-alcoholic fatty liver disease (NAFLD), for which it is running a mid-stage study testing the candidate against Novo Nordisk’s semaglutide. Results from the trial showed that efinopegdutide achieved a significantly greater reduction in liver fat content, while eliciting similar weight loss.

Merck’s strategy of focusing on next-generation oral GLP-1 therapies with additional clinical benefits is meant to help it break into the lucrative obesity market, which many analysts expect to reach $150 billion in value by the early 2030s.

Novo and Eli Lilly are the two early leaders in the obesity space—and are anticipated to control around 80% of the market—but, like Merck, several other biopharma players are vying for a spot in the GLP-1 game. Boehringer Ingelheim is advancing survodutide, which also targets the GLP-1 and glucagon receptors. The candidate is in five Phase III trials, which the pharma launched in 2023.

Boston-based startup Syntis Bio debuted earlier this week to advance alternative obesity treatments that do not operate via the GLP-1 pathway. Its lead program, SYNT-101, blocks the absorption of nutrients in the duodenum and mimics the effects of gastric bypass surgery.

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