Regeneron’s new experimental weight-loss drug cuts muscle loss

Regeneron’s new experimental weight-loss drug halved muscle loss in a trial when given in combination with semaglutide compared to semaglutide alone.

In the study of patients with obesity, the new therapy by Regeneron, which belongs to a different class of drugs to GLP-1 inhibitors, reduced the loss of muscle mass by 50% compared with the loss seen in patients taking Novo’s semaglutide by itself.

The trial results address growing concerns about the significant loss of muscle mass that often accompanies rapid weight loss in patients taking GLP-1 inhibitors.

Successful combination for muscle preservation

The Regeneron drug, trevogrumab, is a monoclonal antibody and works by inhibiting the protein myostatinwhich is closely linked to the loss of muscle mass.

Researchers used MRI scans to measure thigh muscle in patients enrolled in the trial, finding that the addition of a 75-milligram dose of trevogrumab preserved over 70% of ​muscle mass loss compared with semaglutide alone at 52 weeks.

In one part of the two-stage trial, patients taking semaglutide alone lost 6.7% of ​their lean muscle mass over 26 weeks. Those who also took 75 mg of trevogrumab lost ​only 3.3% of ⁠muscle mass while those on 25 mg of trevogrumab lost 4.7% of muscle mass.

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

Data from the trial, which included nearly 1000 participants between the ages of 18 and 65, was presented at the European Association for the Study of Diabetes conference in Milan on Thursday.

Next-generation class of drugs for weight loss

Multiple pharmaceutical companies are now working to produce their own version of this next-generation class of drug, known as anti-myostatin, as the medical community looks for ways to prevent muscle mass loss in patients taking GLP-1 inhibitors.

Analysts forecast that these medicines could reach $30bn in annual sales as soon as 2035.

However, not all drugs have had as successful a start as trevogrumab. Originally, Regeneron’s trial included a second experimental antibody drug, garetosmab.

Two participants receiving higher doses of trevogrumab in combination with garetosmab died within the first 26 weeks of the trial.

The company said that one patient, who had multiple cardiovascular risk factors died from an undetermined cause. The other, who had a history of cardiovascular disease, died by cardiac arrest.

While trevogrumab showed no unexpected side effects, the trevogrumab/garetosmab combination had a high ​rate of adverse side effects, ⁠including muscle spasms.

Despite leading to greater lean-mass preservation than trevogrumab ​alone, Regeneron said it will not move forward with the triple combination.

However, Regeneron has announced that ⁠it has ​selected the 75 mg once-weekly dose of trevogrumab for further studies and plans another mid-stage trial ​in patients over 65.

Boaz Hirshberg, Senior Vice President, Clinical Development Unit Head, Internal Medicine, Regeneron, said: “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.”

He added: “What we want to do is concentrate on the quality of weight reduction. “We want to find the best way to approach ​weight reduction, especially in vulnerable patients.”