Veru Inc. has announced positive topline results from its Phase 2b QUALITY study, demonstrating that enobosarm, when combined with WEGOVY (semaglutide), significantly reduces lean mass loss in overweight or obese patients over 60 years of age. The study, designed to evaluate enobosarm compared to placebo, met its primary goal of preserving lean mass during weight reduction.
The Phase 2b QUALITY study was a multicenter, double-blind, placebo-controlled, randomized, dose-finding study. It involved 168 older patients, all of whom were receiving WEGOVY (semaglutide) for weight reduction. The primary endpoint was the change in total lean body mass from baseline to 16 weeks. Key secondary endpoints included changes in total fat mass, total body weight, and physical function, measured by a stair climb test.
Key Findings from the QUALITY Study
Data from the study revealed that patients on enobosarm lost, on average, 71% less lean mass than patients receiving WEGOVY alone (p=0.002). Additionally, these patients experienced a 27% increase in fat mass loss compared to the WEGOVY-only group. The proportion of subjects that lost ≥10% stair climb power was statistically significant and clinically meaningfully reduced in the enobosarm + semaglutide groups compared to placebo + semaglutide group (p=0.0049).
According to Dr. Louis Aronne, an obesity expert and consultant to Veru, these results are exciting because weight loss typically results in the loss of both lean and fat mass. He emphasized the unmet medical need to preserve muscle and physical function in older patients undergoing weight loss treatments, particularly with GLP-1 receptor agonists. He stated that this is the first clinical study to demonstrate prevention of both lean mass loss and decline in muscle function associated with weight loss in older individuals treated with a GLP-1 RA, potentially benefiting patients with obesity and age-related muscle loss.
Implications for Future Development
Mitchell Steiner, M.D., Chairman, President, and Chief Executive Officer of Veru, stated that the company plans to meet with the FDA to discuss the design of a Phase 3 clinical program, given the promising topline results. The proposed Phase 3 clinical trial design is expected to be a double-blind, placebo-controlled study in older (> 60 years of age), patients who have obesity or who are overweight and who are eligible for treatment with GLP-1 RA. The GLP-1 RA may be either WEGOVY (semaglutide) and/or Zepbound® (tirzepatide). Patients will be randomized to oral daily enobosarm or matching placebo. All subjects will start and receive GLP-1 RA during the study.
The primary objective will be the effect of enobosarm on stair climb power, as measured by the proportion of subjects that lose ≥10% stair climb power from baseline. Proposed key secondary objectives will be to assess the effect of enobosarm on total lean mass, total body weight, total fat mass, bone mineral density, HOMA-IR, and hemoglobin A1c.
Addressing Sarcopenic Obesity
The Phase 2b QUALITY study is the first human study to demonstrate that older patients who are overweight or have obesity and receiving only a WEGOVY (semaglutide) GLP-1 RA are at higher risk for accelerated frailty and functional decline. Lean mass loss in the semaglutide group that did not receive enobosarm was significant as 32% of the total weight loss at 16 weeks was made up of lean mass. Loss of lean mass also matters as 42.6% of patients on placebo + semaglutide had at least a 10% decline in stair climb power. The potential for further reduction in physical function because of ongoing loss of lean mass with chronic GLP-1 RA therapy is worrisome and must be evaluated. The expectation is that all GLP-1 RA containing drugs could cause significant loss of lean mass in older patients raising concerns for potential declines in physical function, mobility disability, functional limitations, and loss of balance with a higher risk for falls and fractures.
Sarcopenic obesity, characterized by the loss of muscle mass and increase in fat mass, affects a significant portion of the older adult population. Veru believes that older patients who have obesity or who are overweight and are receiving a GLP-1 RA are an ideal target population that have demonstrated in the Phase 2b QUALITY clinical study clinical benefit with enobosarm treatment to provide a greater quality weight loss as lean mass and physical function may be preserved with greater and selective loss of adiposity, that is, better body composition weight reduction may be possible. Further, the expectation is that when patients are treated longer with enobosarm, which results in greater loss of adiposity, there would also be a profoundly greater weight reduction than with semaglutide alone.
Safety Profile
While the safety data from the Phase 2b QUALITY study remains blinded, aggregate blinded data have not shown significant differences compared to previous enobosarm studies. Enobosarm has a large safety database, including 27 clinical trials involving 1581 men and women, with some patients dosed for up to 3 years. In this database, enobosarm was generally well-tolerated, with no increases in gastrointestinal side effects, which are already common with GLP-1 RA treatments.
