Weight loss drugs have one big issue; These companies want to fix it

Surging demand for weight loss drugs Wegovy and Zepbound from Novo Nordisk (NVO) and Eli Lilly (NYSE:LLY) has fueled concerns over a significant risk linked to the popular drug class: loss of muscle mass. A growing list of biotechs is racing to address the issue.

While the GLP-1s are good at causing weight loss, some of that weight reduction can come as loss of muscle mass. That can lead to additional concerns, such as injury risk, especially among the elderly, and a potential slowdown of metabolism, which can cause weight regain.

Regeneron’s (NASDAQ:REGN) chief scientific officer, George Yancopoulos, flagged the issue last week when he told The Financial Times that GLP-1s “could be leading to successive changes in body composition that could be creating more harm than good in the long term.”

The Eylea maker is among drug developers attempting to take on the problem by combining GLP-1s with other agents that can negate their effects on muscle tissue.

Regeneron (REGN) is testing an obesity therapy called trevogrumab, which targets muscle growth inhibitor myostatin to address the issue.

A mid-stage trial designed to evaluate the antibody therapy in combination with semaglutide, the active ingredient of Novo’s (NVO) Wegovy, in healthy volunteers and obese patients is currently underway, with its initial data expected in mid-2025.

Regeneron (REGN) is not the only pharmaceutical giant developing myostatin-targeting compounds.

In 2023, Zepbound maker Eli Lilly (LLY) acquired Versanis Bio, a privately held biopharma whose lead asset is bimagrumab, a myostatin-targeting agent. A mid-stage trial to test bimagrumab with semaglutide is currently underway in overweight or obese adults.

Meanwhile, Biohaven’s (BHVN) myostatin-targeting agent, taldefgrobep alfa, has already demonstrated positive preclinical data in increasing lean muscle when used with a GLP-1 receptor agonist. With its Q2 2024 results in August, the company said it would begin a mid-stage trial for taldefgrobep alfa in H2 2024, targeting patients with obesity.

Last month, Scholar Rock (SRRK) completed enrollment in a Phase 2 trial for its myostatin inhibitor apitegromab. The EMBRAZE study is designed to show its proof-of-concept in preserving lean muscle mass in individuals on GLP-1s for obesity.

Several other biotechs offer different mechanisms. Keros Therapeutics’ (KROS) obesity candidate, KER-065, which is designed to increase skeletal muscle and reduce fat mass by inducing the body’s energy expenditure, is currently in Phase 1 development.

Newly-IPO’ed BioAge Labs (BIOA) has started a mid-stage study to test its lead candidate, azelaprag, in combination with LLY’s (LLY) tirzepatide in older adults with obesity. According to BioAge (BIOA), azelaprag, designed to mimic a molecule released during exercise, can restore body composition and muscle function in patients on incretin-based weight loss drugs.

Veru’s (VERU) lead asset, enobosarm, an androgen receptor modulator, is currently undergoing a Phase 2b trial to test its potential as a treatment to preserve muscle and improve fat loss in patients on semaglutide.

The former COVID-19 drug developer said in August that its trial QUALITY has already exceeded the enrollment target and is expected to generate topline data in January 2025.