GTx’s Enobosarm Fails Phase II Trial in Stress Urinary Incontinence; Stock Plunges 90%+

GTx acknowledged today that its sole clinical-phase drug candidate enobosarm has failed a Phase II trial in women with stress urinary incontinence—a failure that sent shares free-falling more than 90% this morning—but stopped short of saying whether it will halt the trial or end clinical development of the drug as a result.

Enobosarm missed its primary endpoint in the Phase II Assessing Enobosarm for Stress Urinary Incontinence Disorder (ASTRID) trial (NCT03241342) of achieving a statistically significant proportion of patients with a greater than 50% reduction in incontinence episodes per day compared to placebo.

The percentage of patients with a greater than 50% reduction after 12 weeks of enobosarm treatment was 58.9% for the 3 mg dose, 57.7% for the 1 mg dose, and 52.7% for placebo, according to top-line results disclosed by GTx.

“We are very disappointed that the ASTRID Trial did not achieve its primary endpoint,” Robert J. Wills, Ph.D., GTx’s executive chairman, said in a statement. “We plan to conduct a full review of all the data.”

Investors responded to the failure announcement will a proverbial stampede that sent shares of GTx on the NASDAQ Capital Market collapsing 94% in premarket trading as of 8:34 a.m. to $1.42 from yesterday’s close of $23.29, before bouncing back somewhat to $2.07, a 91% one-day collapse as of 9:40 a.m., soon after the market opened.

Enobosarm (GTx-024) is a selective androgen receptor modulator (SARM) that along with other GTx SARM compounds has shown increases in pelvic floor muscle mass following treatment in preclinical in vivo data—as well as in a proof-of-concept Phase II clinical trial of the 3 mg dose of enobosarm in postmenopausal women with stress urinary incontinence, a condition that affects up to 35% of adult women.

Positive Proof-of-Concept Data

At the end of the proof-of-concept trial’s 12-week treatment period, GTx said, all 18 enobosarm-treated women showed a clinically meaningful reduction in stress urinary incontinence episodes per day compared to baseline, of at least 50%, the study’s primary endpoint. In addition:

• Mean stress leaks decreased by 81% from baseline.

• Stress leaks decreased from a mean of 5.17 leaks/day at baseline to 1.00 leak/day.

• Median Medical, Epidemiologic and Social Aspects of Aging (MESA) scores for SUI decreased from 79.5% to 44.5%.

Following presentation of that data at the Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction, or SUFU, Winter Meeting, held February 27 – March 3 in Austin, TX, Stifel analyst Adam Walsh raised his price target on GTx stock from $16 a share to $45 a share, maintaining a “buy” rating.

“Key Opinion Leaders, or KOLs, view the off-drug durability of effect data as ‘highly impressive’ and new MRI data ‘strongly supports’ mechanism of action, Walsh told investors,” financial news outlet The Fly reported on March 5.

ASTRID is one of 27 completed or ongoing clinical trials enrolling over 2,200 subjects in which enobosarm has been studied. In those trials, approximately 1,500 subjects were treated with enobosarm at doses ranging from 0.1 mg to 100 mg. At all evaluated dose levels, GTx said, enobosarm was observed to be generally safe and well tolerated.

Enobosarm is also under study as a treatment for breast cancer.

GTx’s pipeline also includes an ongoing preclinical program assessing several preclinical SARD candidates to treat castration-resistant prostate cancer. GTx is developing SARD technology under an exclusive license agreement with the University of Tennessee Research Foundation signed in 2015.

“We are currently on target to have development candidates by year end, which we potentially plan to take into IND-enabling studies,” Dr. Wills added.