Secondary End Point Not Achieved in Phase 3 HERO Study of Relugolix in Advanced Prostate Cancer

September 30, 2020

Among men with advanced prostate cancer, relugolix did not achieve statistical superiority for castration resistance-free survival compared to leuprolide acetate in men with metastatic disease through 48 weeks.

Additional secondary end point results from the phase 3 HERO study evaluating relugolix in men with advanced prostate cancer indicated that relugolix did not achieve statistical superiority for castration resistance-free survival compared to leuprolide acetate (Lupron) in men with metastatic disease through 48 weeks, according to Myovant Sciences, the developer of the agent.

Notably, relugolix at a dose of 120 mg is currently under priority review by the FDA for the treatment of men with advanced prostate cancer, with a target action date set for December 20, 2020.

“These new data from the phase 3 HERO study show that 3 out of 4 men with metastatic prostate cancer remained castration resistance-free through 48 weeks while on oral relugolix, in-line with leuprolide acetate injections, the current standard of care,” Dan George, MD, a professor of medicine and surgery at the Duke University School of Medicine and HERO program steering committee member, said in a press release. “I continue to be excited by relugolix as a potential new and differentiated treatment option for men with prostate cancer given its robust clinical and safety data, including the lower risk of major adverse cardiovascular events compared to leuprolide acetate.”

The randomized, open-label, parallel group, multinational, phase 3 clinical study is designed to evaluate the safety and efficacy of relugolix in over 900 men with androgen-sensitive advanced prostate cancer who required at least 1 year of continuous androgen deprivation therapy. Trial participants were randomized 2:1 to receive either a single loading dose of 360 mg of relugolix followed by 120 mg of relugolix once daily or treatment with a 3-month depot injection of leuprolide acetate.

Castration-resistant prostate cancer was defined by disease progression despite achieving testosterone suppression to castrate levels (< 50 ng/dL). Among the subgroup of men with metastatic disease treated with relugolix, 74% were castration-resistance free through 48 weeks compared to 75% men treated with leuprolide acetate (HR, 1.03; 95% CI, 0.68-1.57; P = .84).

In the secondary end point analysis, castration resistance-free survival was defined as the time from first dose to prostate-specific antigen (PSA) progression per the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria or death from any cause. PSA progression was defined as a PSA increase of 25% or more and at least 2 ng/mL above the nadir; additionally, progression was confirmed by a second PSA value at least 3 weeks later.

Regarding safety, the incidence of adverse events (AEs) in the subgroup of men with metastatic disease was consistent with that previously observed in the primary analysis of HERO with no new safety signals observed.

“We believe the totality of data – including previously reported data from the Phase 3 HERO program, published in the New England Journal of Medicine – presents compelling evidence for the potential use of relugolix in men with advanced prostate cancer,” Lynn Seely, MD, chief executive officer of Myovant Sciences, said in the release. “With our new drug application under priority review by the FDA, we look forward to our target action date in December 2020 and hope to advance our commitment to redefining care by bringing once-daily, oral relugolix to men with prostate cancer.”

Relugolix already met the primary efficacy end point in the phase 3 HERO study, with 96.7% of men treated with relugolix achieving sustained testosterone suppression to castrate levels (< 50 ng/dL) through 48 weeks versus 88.8% of men treated with leuprolide acetate. Moreover, relugolix also met 6 key secondary end points, showing rapid and profound suppression of testosterone and PSA response, in addition to improved testosterone recovery following discontinuation of treatment.

Men randomized to relugolix had a 54% lower risk of major cardiovascular AEs compared to men in the leuprolide acetate group (2.9% vs. 6.2%, respectively). Further, among men with a reported history of major cardiovascular AEs, those treated with relugolix had 80% fewer events reported compared to the leuprolide acetate group (3.6% vs. 17.8%, respectively). Overall though, the incidence of AEs between the 2 groups was comparable (92.9% vs. 93.5%, respectively).

Reference:

Myovant Sciences Announces Results of Additional Secondary Endpoint of Castration Resistance-Free Survival from Phase 3 HERO Study of Relugolix in Advanced Prostate Cancer [news release]. Basel, Switzerland. Published September 29, 2020. Accessed September 29, 2020. https://www.globenewswire.com/news-release/2020/09/29/2100606/0/en/Myovant-Sciences-Announces-Results-of-Additional-Secondary-Endpoint-of-Castration-Resistance-Free-Survival-from-Phase-3-HERO-Study-of-Relugolix-in-Advanced-Prostate-Cancer.html