Regeneron weight-loss drug halves muscle loss in combination with Novo's semaglutide in trial

Sept 30 — An experimental weight-loss drug being developed by Regeneron used in combination with Novo Nordisk's semaglutide reduced the loss of muscle mass by ​50% compared with the loss seen with semaglutide alone in a study of patients with obesity, according to data being presented at a medical meeting.

With the explosive popularity of GLP-1 weight-loss drugs such as Novo's semaglutide, sold as Wegovy ‌for obesity, there has been growing concern about significant loss of muscle accompanying rapidly shed pounds.

The Regeneron drug, trevogrumab, belongs to a different class of medicines that inhibits ⁠the protein myostatin, which is linked to loss of muscle mass.

When ​researchers measured thigh muscle in patients with MRI scans, the ⁠addition of a 75-milligram dose of trevogrumab preserved over 70% of muscle mass loss compared with semaglutide alone at 52 weeks, ‌a summary of the data showed.

"We ‌confirmed that indeed patients that take GLP-1s lose about 30% of their weight in the form of lean ⁠muscle mass, that with trevogrumab we can prevent," said Regeneron executive Boaz Hirshberg, ⁠adding the greatest benefit could potentially be for patients who begin treatment with lower muscle mass.

Data from the trial of nearly 1,000 patients between the ages of 18 and 65 was being presented at the European Association for the Study of Diabetes conference in Milan on Thursday.

Wall Street and the medical community are looking for evidence that next-generation drugs like anti-myostatins can prevent the body from breaking down muscle during weight loss.

At least a dozen companies are working on muscle-preserving therapies, with ‌analysts forecasting the medicines could reach $30 billion in annual sales by 2035.

The multi-pronged trial initially ​included a second experimental Regeneron antibody drug, garetosmab.

In the first 26 weeks, two participants who received higher doses of trevogrumab in combination with garetosmab died. One death was due to an undetermined cause in a patient with multiple cardiovascular risk factors and the second was caused by cardiac arrest in a person with a history of cardiovascular disease, the company said.

Trevogrumab alone showed a safety profile similar to semaglutide, with no unexpected side effects, the company said.

The trevogrumab/garetosmab combination led to greater lean-mass preservation than trevogrumab alone but had a high rate of adverse side effects, including muscle spasms. Regeneron said it will ​not move forward with the triple combination.

The mid-stage study was performed as a two-part trial.

In one part of the trial, patients on semaglutide alone lost 6.7% ‌of their lean ‌muscle mass over 26 ⁠weeks. Those who also took 75 milligrams of trevogrumab lost only 3.3% of muscle mass. The combination with 25 mg of trevogrumab led to 4.7% loss of muscle mass.

When patients stopped semaglutide but kept taking trevogrumab, their muscle mass returned to where it started before the study, suggesting the drug could help rebuild the lost muscle, the company said.

Regeneron said it has selected the 75-mg once-weekly dose for ‌further studies and plans another mid-stage ​trial in patients over 65.

"What we want to do is concentrate on the ‌quality of weight reduction," Regeneron's Hirshberg ⁠said. "We want to find the ​best way to approach weight reduction, especially in vulnerable patients."

(Reporting by Bhanvi Satija in London and Sriparna Roy in Bengaluru; Editing by Caroline Humer ​and Bill Berkrot)

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