Veru Announces Positive Phase IIb Results

Phase IIb QUALITY clinical trial design; The Phase IIb QUALITY clinical study was a multicenter, double-blind, placebo-controlled, randomized, dose-finding study to evaluate the safety and efficacy of enobosarm 3mg, and enobosarm 6mg, compared to placebo in 168 older patients, greater than 60 years of age, who are overweight or have obesity and who are receiving Wegocy (semaglutide), a GLP-1 receptor agonist (RA), for weight reduction. The primary endpoint was the change in total lean body mass from baseline to 16 weeks, and key secondary endpoints were the change from baseline to 16 weeks in total fat mass, total body weight, and physical function as measured by a stair climb test.

In the topline efficacy analysis, the Phase IIb QUALITY clinical study met its primary endpoint with a statistically significant benefit in preservation of total lean body mass in all patients receiving enobosarm + semaglutide versus placebo + semaglutide at 16 weeks.  Secondary endpoints showed:  i.  Enobosarm + semaglutide treatment resulted in a greater reduction in total fat mass compared to placebo + semaglutide at 16 weeks.  ii. There appears to be minor differences in total body weight changes between the enobosarm + semaglutide group and placebo + semaglutide group at 16 weeks. Therefore, enobosarm + semaglutide improved changes in body composition and resulted in more selective and greater loss of fat mass than in subjects receiving placebo + semaglutide. iii. 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.iv. Therefore, enobosarm reduced the proportion of patients that lost clinically significant physical function versus subjects receiving semaglutide alone.

The Company plans to present the full clinical efficacy and safety data set for the Phase IIb QUALITY clinical study in future scientific conferences and publications after the Phase IIb extension portion of study is completed and unblinded.

Dr. Louis Aronne, an obesity expert, past president of the Obesity Society and a scientific advisor and consultant to Veru, who was not directly involved in the QUALITY study stated: “These topline clinical results are very exciting. Weight loss through any modality produces a loss of both lean and fat mass. The greater magnitude of weight loss seen with bariatric surgery and GLP-1 RA based drugs has produced an unmet medical need to preserve muscle and physical function in older patients receiving these treatments. 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. This combined treatment approach could benefit patients with obesity and low amounts of muscle due to age-related muscle loss.”

“Given the promising topline results from the Phase IIb QUALITY clinical trial where enobosarm treatment preserved lean mass, increased fat loss, improved body composition changes, and prevented decline in stair climb physical function in patients receiving Wegovy (semaglutide), we plan to meet with FDA to discuss the design of the Phase III clinical program,” said Mitchell Steiner, M.D., Chairman, President, and Chief Executive Officer of Veru. “The Phase IIb 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.”

“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 IIb 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,” said Gary Barnette Ph.D., Chief Scientific Officer, Veru Inc.

Safety; Safety data remains blinded in the ongoing clinical study and the unblinded safety set will be available when the Phase IIb extension study is done in April 2025. However, the aggregate, blinded data, have not shown significant differences compared to different previous studies of enobosarm. The Independent Data Monitoring Committee also met in October 2024 and evaluated the unblinded safety data with a recommendation to continue the study as planned. As a reminder, enobosarm has a large safety database, which includes 27 clinical trials involving 1581 mostly older men and women, some of which included patients dosed for up to 3 years. In this large safety database, enobosarm was generally well tolerated with no increases in gastrointestinal side effects. This is important as there are already significant and frequent gastrointestinal side effects with a GLP-1 RA treatment alone.

Next regulatory steps; As a reminder, the Phase IIb extension clinical trial where all patients will stop receiving a GLP-1 RA, but will continue taking placebo, enobosarm 3mg, or enobosarm 6mg for an additional 12 weeks is ongoing. The blinded Phase IIb extension clinical trial is asking a different question than the Phase IIb QUALITY clinical study which evaluated the ability of enobosarm to improve body composition changes associated with GLP-1 RA weight loss induction. The Phase IIb extension study will evaluate maintenance of weight loss, meaning whether enobosarm can maintain muscle and prevent the fat and weight gain that occurs after discontinuing a GLP-1 RA. If successful, this would provide another important obesity related indication for which enobosarm could be considered. The topline results for the separate blinded Phase IIb extension clinical study are expected in April of 2025.

As the Phase IIb QUALITY study has positive topline clinical results, we are planning to move forward to request an end of Phase II meeting with FDA. In the new weight reduction FDA guidance, FDA makes a regulatory path distinction between weight reduction drugs and drugs for body composition changes. Based on this updated FDA guidance, enobosarm is being developed as a body composition drug to selectively preserve lean body mass and physical function, and augment loss of fat in older patients who are overweight or have obesity receiving GLP-1 RA containing drug for chronic weight management.