Drugmakers Target Muscle Preservation in New Obesity Treatments
Several pharmaceutical companies are developing novel weight-loss drugs that aim to simultaneously preserve muscle mass. Industry experts, clinical trial specialists, and healthcare professionals emphasize the importance of demonstrating additional health benefits beyond weight loss for these treatments to gain regulatory approval.
Market Potential and Competition
These drugs are intended to complement or replace existing popular weight-loss medications such as Novo Nordisk's Wegovy and Eli Lilly's Zepbound. Trial data have shown that Wegovy and Zepbound can facilitate substantial weight loss (15-20%) but have also raised concerns about muscle loss. Up to 40% of weight loss observed in Wegovy trials was attributed to a reduction in lean mass rather than excess fat.
Approximately a dozen new drugs are currently under development, including those from Eli Lilly, Regeneron, Scholar Rock, and Veru. These drugs primarily target proteins involved in muscle preservation or growth. Veru's enobosarm, tested in a Phase 2 trial, demonstrated a 71% reduction in muscle loss when combined with Wegovy in older patients. Lilly's muscle-preserving drug, bimagrumab, is expected to release data later this year.
Analysts estimate that these new drugs could generate collective revenue ranging from $1 billion to $5 billion annually by the end of the decade. Obesity drug sales are projected to reach $150 billion per year by the early 2030s.
Benefits of Preserved Muscle Mass
Medical professionals suggest that drugs that enhance muscle mass could be particularly beneficial for older or more vulnerable individuals prone to falls and fractures. A higher proportion of muscle mass can also promote sustained weight maintenance, as muscles consume energy even at rest. By addressing muscle preservation, the narrative around weight loss could shift from the amount lost to the duration of weight loss maintenance.
Regulatory Considerations
The Food and Drug Administration's (FDA) stance on evaluating muscle-preserving benefits for regulatory approval is yet to be fully defined. Draft guidelines suggest that lean mass loss is not inherently harmful but recommend measuring participants' muscle-to-fat ratios during trials. The FDA has advised companies testing muscle-preserving drugs to engage with the agency early on to discuss their chosen methodologies.
Analysts and experts express skepticism about the FDA approving a drug solely based on its muscle-mass preservation effects. However, they believe that demonstrating additional benefits such as reduced side effects or improved cardiovascular health could enhance approval prospects. Veru's drug, for instance, has shown promise in maintaining patients' ability to climb stairs, a benefit recognized by the FDA for other therapeutic classes.
Targeting Muscle Growth
Veru's drug targets androgen receptor cells to stimulate muscle growth, and its late-stage trial will assess stair climbing ability as a primary endpoint. Lilly is evaluating bimagrumab both independently and in combination with Zepbound and Wegovy. The company aims to demonstrate incremental weight loss or functional benefits from lean mass preservation to support the combination therapy approach.
Approximately half of the new drugs target myostatin, a protein associated with muscle growth, while others focus on activin, a protein with various biological functions. Initially developed for neuromuscular disorders, these drugs are believed to promote muscle growth and reduce fat by consuming stored energy.
Combination Therapies and Future Research
Experts suggest that combining myostatin drugs with GLP-1 agonists could optimize efficacy and reduce side effects. BioHaven's drug, for instance, increased lean mass and bone density compared to placebo but did not improve motor function in spinal muscular atrophy patients. The company is now planning a mid-stage trial for obesity.
Analysts and investors are closely following the progress of Lilly's bimagrumab and Regeneron's trevogrumab, which are currently in mid-stage studies. Regeneron's drug is being tested independently and in combination with Wegovy. Scholar Rock is targeting a change in lean body mass in its trial for apitegromab.
Clinical Impact
Successful drug development in this area requires evidence of not only structural muscle changes but also improvements in physical performance. Healthcare practitioners emphasize the importance of demonstrating functional benefits for patients, such as enhanced mobility and reduced fall risk.