Myovant Sciences announced positive top-line results from SPIRIT 1, the second of two Phase 3 studies of once-daily relugolix combination therapy (relugolix 40 mg plus estradiol 1.0 mg and norethindrone acetate 0.5 mg) in women with pain associated with endometriosis. Relugolix combination therapy met its co-primary efficacy endpoints and all seven key secondary endpoints in the SPIRIT 1 study. In addition, relugolix combination therapy was generally well-tolerated and resulted in minimal bone mineral density loss over 24 weeks. These data are consistent with SPIRIT 2, the results of which were announced in April of 2020.
SPIRIT 1 was a randomized, double-blind, placebo-controlled study to evaluate 24 weeks of oral, once-daily relugolix (40 mg) co-administered with either 12 or 24 weeks of low-dose estradiol (1.0 mg) and norethindrone acetate (0.5 mg), compared with placebo. The study enrolled 600 women with endometriosis-associated pain. Relugolix combination therapy achieved both co-primary endpoints by demonstrating clinically-meaningful pain reductions for 74.5% of women with dysmenorrhea (menstrual pain) and 58.5% of women with non-menstrual pelvic pain, compared to 26.9% and 39.6% of women in the placebo group, respectively. On average, women receiving relugolix combination therapy had a 73.3% reduction on the 11-point (0 to 10) Numerical Rating Scale for dysmenorrhea from 7.3 (severe pain) to 1.8 (mild pain). All seven key secondary endpoints measured at Week 24 and compared to placebo achieved statistical significance, including changes in mean dysmenorrhea and overall pelvic pain, impact of pain on daily activities as measured by the Endometriosis Health Profile-30 (EHP-30) pain domain, greater proportions of women not using analgesics, changes in mean non-menstrual pelvic pain, greater proportions of women not using opioids and changes in mean dyspareunia (painful intercourse). The only reported adverse events in at least 10% of women in the relugolix combination group were headache and hot flashes.
“Relugolix has now achieved positive results in five Phase 3 studies across three indications, demonstrating its potential to benefit women with pain from endometriosis and women with heavy menstrual bleeding from uterine fibroids as well as men with advanced prostate cancer,” said Juan Camilo Arjona Ferreira, M.D., chief medical officer of Myovant Sciences. “We look forward to sharing the one-year data from the SPIRIT extension study and submitting a New Drug Application to the FDA for this one dose, one pill, once a day potential treatment for women with endometriosis, which would be our third NDA submission in short succession.”
Relugolix is a once-daily, oral gonadotropin-releasing hormone (GnRH) receptor antagonist that reduces production of ovarian estradiol, a hormone known to stimulate the growth of uterine fibroids and endometriosis, and testicular testosterone, a hormone known to stimulate the growth of prostate cancer. Myovant is also developing relugolix as a monotherapy tablet (120 mg once daily) for men with advanced prostate cancer.
Endometriosis is an estrogen-dependent, inflammatory disease in which tissue similar to the uterine lining is found outside the uterine cavity, commonly in the lower abdomen or pelvis, on ovaries, the bladder, and the colon. This endometrial-like tissue outside the uterus results in chronic inflammation and can cause scarring and adhesions. The symptoms associated with endometriosis include painful periods and chronic pelvic pain, painful ovulation, pain during or after sexual intercourse, heavy bleeding, fatigue, and infertility. For endometriosis-associated pain, initial treatment options include hormonal contraceptives and over-the-counter pain medications. In more severe cases, GnRH agonists such as leuprolide acetate are used for short-term treatment. An estimated six million women in the U.S. suffer from symptoms of endometriosis, and an estimated one million women are inadequately treated by current medical therapy and require further treatment. Almost 200 million women are affected globally.