The Food and Drug Administration has accepted for review the supplemental New Drug Application for relugolix in combination with estradiol and norethindrone acetate (Myfembree) for the management of moderate to severe pain associated with endometriosis.
The application is supported by data from the phase 3 SPIRIT program, which includes the SPIRIT 1 (ClinicalTrials.gov Identifier: NCT03204318) and SPIRIT 2 (ClinicalTrials.gov Identifier: NCT03204331) studies, as well as an open-label extension study (ClinicalTrials.gov Identifier: NCT03654274). The 24-week, double-blind, placebo-controlled SPIRIT 1 and 2 studies evaluated the efficacy and safety of relugolix plus combination therapy (estradiol 1mg and norethindrone acetate 0.5mg) in more than 1200 women with pain associated with endometriosis.
Patients were randomly assigned to receive relugolix 40mg once daily plus combination therapy, relugolix 40g once daily monotherapy for 12 weeks followed by relugolix combination therapy for an additional 12 weeks, or placebo. The primary outcome measures were the percentage of patients who met the dysmenorrhea and non-menstrual pelvic pain responder criteria at week 24 or at the end of treatment.
Results from both studies showed that compared with placebo, a greater proportion of patients treated with relugolix combination therapy had clinically meaningful reductions in dysmenorrhea (SPIRIT 1: 74.5% vs 26.9%; SPIRIT 2: 75.2% vs 30.4%; P <.0001) and non-menstrual pelvic pain (SPIRIT 1: 58.5% vs 39.6%; SPIRIT 2: 66.0% vs 42.7%; P <.0001).
By week 8, dysmenorrhea decreased from severe at baseline to mild in the relugolix combination therapy arm; this effect was sustained through week 24. Both studies also met key secondary endpoints including reduction in dyspareunia and improvement on the Endometriosis Health Profile-30 (EHP-30) pain score.
The SPIRIT extension study evaluated the long-term efficacy and safety of relugolix combination therapy over 52 weeks among eligible women who completed either the SPIRIT 1 or 2 studies. Findings showed that 84.8% and 73.3% of women reported clinically meaningful reductions in dysmenorrhea and non-menstrual pelvic pain, respectively, at 1 year.
Myfembree is currently approved for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women. A decision on the endometriosis indication is expected on May 6, 2022.
- Myovant Sciences and Pfizer announce FDA acceptance of supplemental New Drug Application for Myfembree® for the management of moderate to severe pain associated with endometriosis. News release. Myovant Sciences and Pfizer Inc. Accessed September 9, 2021. https://investors.myovant.com/news-releases/news-release-details/myovant-sciences-and-pfizer-announce-fda-acceptance-supplemental.
- Myovant Sciences and Pfizer announce positive one-year data from phase 3 SPIRIT extension study of once-daily relugolix combination therapy in women with endometriosis. News release. Myovant Sciences and Pfizer Inc. January 26, 2021. Accessed September 9, 2021. https://investors.myovant.com/news-releases/news-release-details/myovant-sciences-and-pfizer-announce-positive-one-year-data.
- Myovant Sciences presents additional data on relugolix combination therapy from studies in endometriosis and uterine fibroids. News release. Myovant Sciences and Pfizer Inc. October 21, 2020. Accessed September 9, 2021. https://investors.myovant.com/news-releases/news-release-details/myovant-sciences-presents-additional-data-relugolix-0.