Combination Regimen Reduces Pain for Women with Endometriosis

Findings from a Phase III long-term extension study show a once-daily therapy consisting of relugolix with estradiol and norethindrone acetate leads to clinically meaningful reductions in menstrual pain and non-menstrual pelvic pain over one year in women with endometriosis.

The study was part of Myovant Sciences and Pfizer’s SPIRIT trial, which investigated the use of relugolix 40 mg plus estradiol 1.0 mg and norethindrone acetate 0.5 mg in women with endometriosis over 52 weeks.

Myovant and Pfizer entered into a collaborative agreement in December, which was aimed to develop and commercialize relugolix in both oncology and women’s health in the U.S. and Canada. The two companies also plan to develop and commercialize relugolix in advanced prostate cancer.

If approved, Myovant Sciences and Pfizer will also seek to develop a combination regimen with relugolix, estradiol and norethindrone acetate in uterine fibroids and endometriosis.

In the Phase III trial, the two companies sought to assess their relugolix combination treatment in endometriosis, an estrogen-dependent, inflammatory disease. In this disease, endometrial-like tissue found outside the uterine cavity leads to chronic inflammation and ultimately scarring and adhesions.

The positive findings from the extension study, which are considered consistent with efficacy and safety data in the Phase III SPIRIT 1 and SPIRIT 2 studies, will be used in a New Drug Application submitted to the U.S. Food and Drug Administration, which is expected to be submitted in the first half of 2021.

“Given the debilitating impact that endometriosis can have on women in their daily lives, often over many years, we need non-invasive and long-term treatment options,” according to a statement made by Linda Giudice, M.D., Ph.D., Distinguished Professor in the Center for Reproductive Sciences at the University of California, San Francisco (UCSF) and SPIRIT Program Steering Committee Member. “The one-year data from the Phase 3 SPIRIT extension study offers promising evidence that relugolix combination therapy has the potential to significantly and durably reduce pain in women with endometriosis, while remaining well tolerated.”

Clinically meaningful reductions in dysmenorrhea and non-menstrual pelvic pain were reported in 84.8% and 73.3% of women, respectively, who received the relugolix combination treatment over the one-year study period. Over 52 weeks, women reported a mean 82.8% reduction on the 11-point Numerical Rating Scale (0-10) for dysmenorrhea from 7.4 (severe pain) to 1.3 (mild pain).

“Building on the strength of our one-year data of relugolix combination therapy in uterine fibroids, we are pleased by the one-year safety and efficacy data in women with endometriosis, which further our vision for a one pill, once-a-day treatment option suitable for long-term use in both diseases,” said Myovant Sciences’ Chief Medical Officer Juan Camilo Arjona Ferreira, M.D. “We look forward to submitting a New Drug Application for this potential new treatment for women with endometriosis in the first half of this year.”

Throughout the study, the investigators observed relatively stable bone mineral density in all patients treated with the combination therapy. There was only minimal yet non-clinically meaningful bone loss through week 24. No new safety signals were found with the treatment compared with safety findings from the SPIRIT 1 and SPIRIT 2 studies. Commonly reported adverse events (≥10 participants) in the active treatment group included headache, nasopharyngitis, and hot flashes.