GTx’s lead candidate, enobosarm, did not meet its primary endpoint in a phase 2 trial involving post-menopausal women with stress urinary incontinence (SUI). More patients treated with the drug reported fewer incontinence episodes than did patients on placebo, but the difference wasn’t big enough to call the study a success.
Enobosarm is a selective androgen receptor modulator (SARM) that GTx is testing in SUI and breast cancer. The drug binds to androgen receptors on the membrane of the cell’s nucleus, allowing it to activate or inhibit nuclear activity. GTx is using it to target androgen receptor-positive breast cancers as well as SUI, which is caused by weakened or dysfunctional muscles that support the bladder.
The primary endpoint of the phase 2 trial was the proportion of patients who had a greater than 50% decrease in incontinence episodes per day compared to placebo. Topline data showed that after 12 weeks, 53% of patients on placebo achieved this reduction. That number was 59% for patients receiving a 3-mg dose of enobosarm and 58% for those on the 1-mg dose—in other words, enobosarm’s performance was not statistically significant.
“We are very disappointed that the ASTRID Trial did not achieve its primary endpoint,” said Robert J. Wills, Ph.D., executive chairman of GTx. “We plan to conduct a full review of all the data. We want to thank the patients, physicians, study coordinators and the entire GTx team for their support of this novel study. We have an ongoing preclinical program assessing the potential of SARDs, our novel selective androgen receptor degrader technology, to treat castration-resistant prostate cancer. We are currently on target to have development candidates by year end, which we potentially plan to take into IND-enabling studies.”
Like SARMs, SARDs bind to androgen receptors, but go one step further—they are designed to trigger androgen receptor degradation. This ultimately inhibits tumor cell proliferation in androgen-dependent prostate cancer cell lines, GTx said. The company is developing its SARD candidate as a potential treatment for men with castration-resistant prostate cancer, including those whose cancer is treatment-resistant.