Successful LIBERTY 1 study of relugolix meets primary efficacy endpoint in women with uterine fibroids

Myovant Sciences announced that LIBERTY 1, the first of two Phase III studies of once daily relugolix combination therapy met its primary efficacy endpoint and six key secondary endpoints in women with uterine fibroids. Relugolix combination therapy maintained bone mineral density at levels comparable to placebo over 24 weeks and was generally well tolerated.

In the primary endpoint analysis, 73.4% of women receiving once daily oral relugolix combination therapy achieved the responder criteria compared with 18.9% of women receiving placebo (p < 0.0001). A response was defined as a menstrual blood loss volume of less than 80 mL and a 50 percent or greater reduction from baseline in menstrual blood loss volume during the last 35 days of the 24-week treatment period measured using the alkaline hematin method. On average, women receiving relugolix combination therapy experienced an 84.3% reduction in menstrual blood loss from baseline, a clinically relevant key secondary endpoint. Bone mineral density was comparable between the relugolix combination and placebo groups. The distribution of the change in bone mineral density, including outliers, was similar for the relugolix combination therapy and placebo groups at 24 weeks, as assessed by dual energy x-ray absorptiometry (DXA).

The 24-week study achieved six key secondary endpoints with statistical significance compared to placebo including mean change in menstrual blood loss from baseline to week 24, reduction in pain in women with pain at baseline, improvement in quality of life, amenorrhea defined as no or negligible blood loss, improvement in anemia in those women with anemia at baseline, and reduction in uterine volume. The overall incidence of adverse events in the relugolix combination and placebo groups was comparable (62% vs. 66%). In the relugolix combination therapy group 5% of women discontinued treatment early due to adverse events compared with 4% in the placebo group.

The only adverse event in the relugolix combination arm occurring in at least 10% of women and more frequently than in the placebo arm was hot flush (11% versus 8%). There were no pregnancies in the relugolix combination group and one in the placebo group.

Myovant expects data from LIBERTY 2, the replicate Phase III study evaluating once daily relugolix combination therapy in women with uterine fibroids and heavy menstrual bleeding, in the third quarter of 2019 and, provided the LIBERTY 2 study is successful, plans to submit a New Drug Application (NDA) to the FDA in the fourth quarter of 2019.

Comment: Relugolix is a once daily oral gonadotropin-releasing hormone (GnRH) receptor antagonist that reduces ovarian estradiol production, a hormone known to stimulate the growth of uterine fibroids. Myovant is also studying relugolix combination therapy (relugolix 40 mg plus 1.0 mg estradiol with 0.5 mg norethindrone acetate) in two Phase III clinical studies (SPIRIT 1 and SPIRIT 2) evaluating endometriosis-associated pain. Relugolix monotherapy, 120 mg once daily, is also being evaluated in a Phase III HERO study in men with advanced prostate cancer.