Regeneron and Lilly Struggle with Clinical Objectives after Market Focus on Weight Reduction

Enhancing the quality of weight loss is the next area of focus for pharmaceutical companies in the obesity field. Novo Nordisk’s Wegovy and Eli Lilly’s Zepbound, two licensed GLP-1 medications, promote lean muscle loss and the desired overall weight loss in patients.

George Yancopoulos, Chief Scientific Officer of Regeneron, responded during the company’s first-quarter earnings conference. In a phase 2 study, Novo’s semaglutide (marketed as Wegovy for weight reduction) will be combined with trevogrumab either with or without Regeneron’s bone disease candidate, garetosmab. The idea is to see whether the combination can enhance weight reduction and/or help people keep off semaglutide after they stop taking it.

Yancopoulos stated that their initial goal is to see whether the combination leads to a greater rate of weight reduction. The CEO said that this might be the simplest regulatory endpoint of all.

Yancopoulos noted that if muscle mass stays the same but fat loss rises, endpoints might be found in metabolic markers like maintenance of function, which is used in the diabetes sector. Naturally, that’s how medications like Zepbound and Wegovy, which are sold as Ozempic and Mounjaro in the diabetic industry got their start.

The company believes that merely demonstrating the nature of the weight reduction in terms of fat versus muscle is the most crucial aspect of the phase 2 trial. In the end, patients must benefit considerably more from maintaining muscle mass and accelerating fat loss, as doing so may prevent many of the disastrous long-term repercussions of widespread GLP-1 usage.

Patient enrollment in the mid-phase trevogrumab study is anticipated to start in the middle of 2024, as previously indicated by Regeneron. A trial assessing a high dosage of trevogrumab in healthy volunteers is fully enrolled.

Daniel Skovronsky, chief scientific officer and president of Lilly Research Laboratories & Lilly Immunology, addressed a similar issue regarding his company’s upcoming muscle-preserving weight loss medication, bimagrumab.

“Compared to incretins, bimagrumab has a very different mechanism of weight loss, but we think it could be important when combined with incretins,” Skovronsky stated. In July 2023, Lilly purchased bimagrumab by acquiring Versanis Bio for $1.9 billion.

In a phase 2 study, the monoclonal antibody is being investigated in conjunction with semaglutide, and it binds the activin/myostatin type II receptors ActRIIA and ActRIIB. The purpose of the trial is to determine if bimagrumab can maintain or grow muscle mass in response to weight reduction or fat loss. The main outcome is the change in baseline body weight at 48 weeks. Secondary endpoints include changes in lean mass, body mass index, HbA1c, visceral adipose tissue, total body fat mass, body fat percentage, and quality of life.

When bimagrumab is used with an incretin medication such as semaglutide, Lilly hopes to see a change in adipose tissue or body fat and muscle mass, particularly an increase in the ratio of lean-to-fat mass.

Similar secondary outcomes to Lilly’s test are found in Regeneron’s phase 2 trial. These include changes in body weight, thigh muscle volume, lean mass, waist circumference, and physical function. Yancopoulos thinks that maintaining muscle mass is still more important than losing weight overall.