With GLP-1-related drugs having won the race to weight loss approval, attention at many obesity-focused biopharmas has turned to the trickier task of finding a way to lose fat while retaining muscle.
Veru is one biotech that thinks it’s found an answer. The Miami-based company has been testing two doses of its oral selective androgen receptor modulator enobosarm in a phase 2b trial of 168 patients aged over 60 years who are overweight or with obesity who are already receiving Novo Nordisk’s blockbuster weight loss drug Wegovy.
The drug, while heralded as a strong weight loss drug, has however been associated with lean mass loss of up to 40% at the end of 68 weeks.
The enobosarm study hit its primary endpoint of showing a statistically significant preservation of total lean body mass at 16 weeks in patients receiving enobosarm compared to those who received placebo, Veru said in a Jan. 27 release.
Specifically, while the placebo cohort saw a mean loss of lean mass—body weight that excludes fat—of 4.1%, individuals taking enobosarm only saw a 1.2% reduction in lean mass. When it came to secondary endpoints, the enobosarm group also saw a greater reduction in total fat mass, of 10.9%, compared to the 8.6% reduction in the placebo cohort.
Investors had a mixed reaction to the results, initially sending the company’s stock up before driving it down 35% to 77 cents in premarket trading Monday compared with a Friday closing price of $1.21.
In this morning’s release, Veru also pointed to a statistically significant reduction in the number of patients who lost more than 10% of their ability to climb stairs, with 19.4% of enobosarm patients experiencing this compared to 31.9% of the placebo group.
Addressing this specific finding, Veru CEO Mitchell Steiner, M.D., said 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,” Steiner added.
Veru licensed enobosarm in 2020 from GTx, which had failed to show its potential to treat stress urinary incontinence but had more luck demonstrating potential in breast cancer. Based on this morning’s results, Veru is now planning to meet with the FDA to agree on the design of a phase 3 trial.
“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,” Steiner said.
The safety data from the trial remain blinded for now, although Veru said the latest study had not shown significant differences to previous trials of enobosarm.
A number of other biopharmas are chasing the same holy grail of reducing weight without losing muscle. They include Altimmune and Rivus Pharmaceuticals, which both unveiled phase 2 data last year showing that their weight loss candidates could preserve muscle.
Meanwhile, Roche is hoping that combining an injectable dual GLP-1/GIP receptor agonist acquired from Carmot alongside its own anti-myostatin antibody could also help patients reduce the muscle loss typically associated with losing weight.