The FDA has cleared Veru’s Investigational New Drug (IND) application for its Phase 2b clinical study to evaluate enobosarm, an oral novel selective androgen receptor modulator (SARM), to preserve muscle mass and physical function and further increase fat loss in patients receiving a Glucagon-like peptide-1 receptor agonist (GLP-1 RA) drug for potentially higher quality weight loss.
GLP-1 RA drugs are very effective drugs that result in significant weight loss. Unfortunately, studies have shown that up to 50% of the total weight loss comes from muscle which is problematic as muscle is essential for metabolism, strength, and physical function.
The Phase 2b, multi-centre, double-blind, placebo-controlled, randomised, dose-finding clinical trial is designed to evaluate the safety and efficacy of enobosarm 3mg, enobosarm 6mg or placebo as a treatment to augment fat loss and to prevent muscle loss in 90 sarcopenic obese or overweight elderly patients receiving a GLP-1 RA who are at-risk for developing muscle atrophy and muscle weakness. The primary endpoint is lean body mass (muscle) and the key secondary endpoint is total body fat mass at 16 weeks. The clinical study is expected to begin by April 2024 with the topline clinical results from the trial expected in the end of the fourth calendar quarter of 2024.
After completing the efficacy dose-finding portion of the Phase 2b clinical trial, participants will then continue into an open label extension trial where all patients will receive 6mg of enobosarm monotherapy for 12 weeks to determine the ability of enobosarm to rescue, or reverse muscle loss and prevent fat and weight rebound after stopping a GLP-1 RA. The results of the separate Phase 2b open label extension clinical study is expected in calendar Q2 2025.
“FDA clearance of our IND will allow us to evaluate enobosarm as a combination treatment with GLP-1 drugs to prevent the loss of muscle, while preferentially reducing fat in not only overweight or obese patients, but especially for the large subpopulation of sarcopenic obese or overweight elderly patients who are at-risk for developing muscle atrophy and muscle weakness leading to frailty,” said Dr Mitchell Steiner, Chairman, President and Chief Executive Officer of Veru. “We look forward to starting the Phase 2 clinical study to further validate enobosarm’s ability to preserve muscle and physical function while augmenting fat loss to provide for a potentially higher quality weight loss.”
According to the CDC, 41.5% of older adults have obesity in the US and could benefit from a weight loss medication. Up to 34.4% of these obese patients over the age of 60 have sarcopenic obesity. This large subpopulation of sarcopenic obese patients is especially at risk for taking GLP-1 drugs for weight loss as they already have critically low amount of muscle due to age-related muscle loss.
Further loss of muscle mass when taking a GLP-1 RA medication may lead to muscle weakness leading to poor balance, decreased gait speed, mobility disability, loss of independence, falls, bone fractures and increased mortality which is a condition like age-related frailty. Because of the magnitude and speed of muscle loss while on GLP-1 RA therapy for weight loss, GLP-1 RA drugs may accelerate the development of frailty in older obese or overweight elderly patients.
Enobosarm (aka ostarine, MK-2866, GTx-024, and VERU-024), a novel oral daily selective androgen receptor modulator (SARM), has been previously studied in five clinical studies involving 968 older normal men and postmenopausal women as well as older patients who have muscle wasting because of advanced cancer. Advanced cancer simulates a “starvation state” where there is significant unintentional loss or wasting of both muscle and fat mass similar to what is observed with GLP-1 RA treatment.
The totality of the clinical data from these five clinical trials demonstrates that enobosarm treatment leads to dose-dependent increases in muscle mass with improvements in physical function as well as significant dose-dependent reductions in fat mass. The patient data that were generated from these five enobosarm clinical trials in both elderly patients and in patients with a cancer induced starvation-like state provide strong clinical rationale for enobosarm. The expectation is that enobosarm in combination with a GLP-1 RA would potentially augment the fat reduction and total weight loss while avoiding muscle loss.
In addition, enobosarm has a large safety database, which includes 27 clinical trials involving 1581 men and women dosed with duration of treatment in some patients for up to three years. In this large safety database, enobosarm was generally well tolerated with no increase in gastrointestinal side effects. This is important as there are already significant and frequent gastrointestinal side effects with a GLP-1 RA treatment alone.