The race to develop the next blockbuster obesity drug is intensifying, with Novo Nordisk and Eli Lilly leading the charge. Numerous companies are vying to create more effective, convenient, and tolerable treatments than Wegovy and Zepbound. Several key trial readouts expected in the coming months will shape the future of this competitive market.
Zepbound vs. Wegovy: A Head-to-Head Showdown
Eli Lilly's SURMOUNT-5 trial directly compares Zepbound to Wegovy in 700 participants with obesity or overweight and related complications. The results, anticipated by the end of the year, could influence physician and patient preferences. Zepbound has demonstrated up to 21% body weight loss in previous trials, compared to Wegovy's 16%. A positive outcome could propel Lilly's market valuation past $1 trillion. However, Lilly is still awaiting results from the SURPASS-CVOT trial to prove Zepbound's ability to prevent cardiovascular complications, a benefit already demonstrated by Wegovy.
Novo Nordisk's Dual Agonist: Cagrisema
Novo Nordisk is developing cagrisema, a dual-acting drug combining semaglutide (the active ingredient in Wegovy) with an amylin analogue. The Phase 3 REDEFINE1 trial, involving approximately 3,400 participants, is expected to generate data in the fourth quarter. This trial compares cagrisema against placebo and Wegovy over 68 weeks. The results will provide insights into cagrisema's potential against Zepbound, especially after the SURMOUNT-5 data is released. Novo Nordisk is also directly comparing cagrisema to Zepbound in another trial, with data expected next year.
Amgen's Monthly Contender: MariTide
Amgen's maridebart cafraglutide (MariTide) is a monthly injectable targeting both GLP-1 and GIP, similar to Zepbound. However, MariTide inhibits GIP rather than stimulating it. Phase 2 results, measuring weight loss over 52 weeks in nearly 600 participants with obesity (some with diabetes), are expected by the end of the year. Early Phase 1 data suggested MariTide might induce the most weight loss over 12 weeks among tested drugs.
The Rise of Obesity Pills
While Novo Nordisk and Eli Lilly are developing oral versions of their injectable drugs, other companies are focusing on oral medications. Roche acquired Carmot Therapeutics for $2.7 billion to gain access to obesity drugs, including the GLP-1 pill CT-996. A Phase 1 dosing trial of CT-996 is expected to conclude by November, providing insights into its biological activity, safety, and weight loss potential. Other companies like Pfizer, Structure Therapeutics, Terns Pharmaceuticals and Viking Therapeutics are also advancing oral obesity drugs.
Preserving Muscle Mass During Weight Loss
The rapid weight loss induced by GLP-1 agonists can lead to muscle loss, which can negatively impact metabolism and long-term weight management. Veru is conducting a Phase 2 trial of enobosarm (Ostarine), a muscle-building drug, in combination with Wegovy in older adults with obesity and muscle loss. The trial will measure changes in muscle mass and physical function over 16 weeks, with results expected by the end of the year.
Exploring New Drug Targets: CB1 Inhibition
Beyond GLP-1 and GIP, other treatment approaches are being investigated. Skye Bioscience is developing nimacimab, a CB1 inhibitor, to modulate appetite and inflammation. Interim Phase 2 results from the CBEYOND trial, comparing nimacimab to placebo and Wegovy, are expected by mid-2025. The trial will measure weight loss over 26 weeks in 120 participants.
