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Obesity drugs’ success spurs rush in muscle-preserving drug research

March 13, 2024

Glucagon-like peptide 1 (GLP-1) agonists help patients shed fat, but also lead to the loss of lean mass from bones, organs, and muscles. Consequently, companies across industries are hoping to capitalize on the opportunity to combat this side effect and introduce novel therapies. The luxury gym Equinox debuted a GLP-1 protocol, a personal training program designed to help members preserve muscle mass; and the meal delivery service Daily Harvest offers a GLP-1 meal collection that includes high protein selections to offset muscle loss. In the biopharma space, companies are hoping to solve the vexing muscle loss problem by introducing novel therapies that both induce weight loss and promote lean mass retention. (Arnold, 2024; Gagne, 2024; Meyersohn, 2024)

Potential patient impact

The loss of lean muscle, particularly in older adults, can lead to an increased risk of injury or even the slowing of metabolism, leading to weight regain. With few exceptions, the loss of muscle mass naturally begins to deplete around age 30. After that, adults lose as much as 3% to 5% of muscle mass each decade, with the process accelerating after age 60. GLP-1s can induce the same loss of muscle mass, but often in a drastically condensed period. In the past, muscle mass loss has been seen as a symptom of aging or a chronic condition rather than a standalone condition that could be treated. The standard of care hasn’t changed in years and includes strength training and nutritional counseling, both of which can be effective but are often limited by comorbidities such as chronic illnesses, injuries, and inflammation. (Arnold, 2024; Gatlin, 2024)

Biopharma companies advancing new treatments

Drug companies are experimenting with drugs originally designed to preserve or regenerate skeletal muscle for treating muscle atrophy in degenerative diseases or aging in combination with GLP-1 agonists used for obesity to spare lean muscle. Many of these muscle-building agents are behind major acquisitions, including Eli Lilly’s acquisition of Versanis Bio and its drug bimagrumab, a monoclonal antibody that is now going through phase 2b trials in combination with Ozempic. In the company’s phase 2 trial, researchers found that the cohort of individuals with overweight or obesity and had type 2 diabetes and took bimagrumab decreased their total body fat mass by 20.5% and lean mass increased by 3.6%. Additionally, when patients stopped taking the drug, they didn’t regain any weight over 12 weeks, whereas the company said patients who stopped taking other weight-loss drugs experienced rapid weight gain. (Arnold, 2024; Gatlin, 2024)

Lilly is also working with BioAge Lab, whose drug is designed to mimic a protein that the body makes more of during exercise to improve metabolism and muscle function. In February 2024, BioAge Lab secured $170 million in Series D funding, which it says will allow the company to combine its apelin receptor agonist azelaprag (BGE-105) with Lilly’s Mounjaro (tirzepatide) in phase 2 studies. In phase 1 studies, the combination was shown to preserve lean body tissue and boosted weight loss by 10% to 15% in healthy adults aged 65 and up compared with Mounjaro alone. (Arnold, 2024; Gatlin, 2024)

Connecticut-based Biohaven’s myostatin inhibitor, taldefgrobep alfa, helps the body grow muscle. The company’s studies in spinal muscular atrophy appear promising; it says the drug led to weight loss and increased lean tissue in preclinical animal testing. Biohaven is turning its attention to obesity and expects to start a phase 2 study of taldefgrobep alfa as a weight-loss drug, testing it both alone and in conjunction with a GLP-1 based drug. (Bilodeau, 2024) Similarly, Juvena Therapeutics is advancing its lead drug for myotonic dystrophy Type 1 and says that it expects this or a similar compound emerging from its discovery pipeline could be combined with incretin to preserve muscle. And Regeneron intends to launch a phase 2 trial pairing the company’s muscle-preserving monoclonal antibodies, trevogrumab and garetosmab, alongside Novo Nordisk’s Ozempic (semaglutide). (Arnold, 2024; Gatlin, 2024)

Another approach on the horizon includes targeting genes in the muscles. Arrowhead Pharmaceuticals is testing two treatments that are used in muscular dystrophy but could be used against lean muscle mass loss associated with GLP-1 drugs. In the near term, Arrowhead has indicated it may focus on developing adipose drug candidates. (Gatlin, 2024)

Sources:

Arnold, C. (2024, March 5). Nat Biotechnol. After obesity drugs’ success, companies rush to preserve skeletal muscle. https://pubmed.ncbi.nlm.nih.gov/38443623/

Bilodeau, K. (2023, November 20). BioPharma Dive. Biohaven hopes to muscle in on Ozempic with a different type of weight loss drug. https://www.biopharmadive.com/news/glp-1-biohaven-weight-loss-lean-muscle-ozempic/700290/

Gagne, Y. (2024, January 27). Fast Company. Daily Harvest is now making Ozempic-friendly mealshttps://www.fastcompany.com/91017829/daily-harvest-ozempic-friendly-meals

Gatlin, A. (2024, February 23). Investor’s Business Daily. Weight-loss drugs have one big problem. These drugmakers are taking it on. https://www.investors.com/news/technology/weight-loss-drugs-how-outliers-like-biohaven-regeneron-are-trying-to-squeeze-into-the-obesity-space/

Meyersohn, N. (2024, March 8). CNN Business. Ozempic is coming for gyms. Here’s how they’re responding. https://www.cnn.com/2024/03/01/business/ozempic-wegovy-equinox-life-time-gyms/index.html