Myovant and Pfizer Report Positive Phase 3 Data for Relugolix Combination Therapy in Endometriosis

Compiled by Fan Dongdong

Recently, according to the latest results from a Phase III long-term extension study published by Pfizer and Myovant Sciences, the combination therapy of once-daily relugolix, estradiol, and norethisterone acetate can achieve clinically significant symptom relief in women with endometriosis within one year, reducing both dysmenorrhea and non-menstrual pelvic pain.

Last December, Pfizer announced a collaboration with Myovant Sciences to jointly develop and commercialize the oral gonadotropin-releasing hormone (GnRH) receptor antagonist relugolix in the United States and Canada for the treatment of oncology and women’s health conditions. Under this agreement, Myovant is eligible to receive up to $4.2 billion in payments, including an upfront payment of $650 million. This trial is part of the SPIRIT trial conducted by Myovant and Pfizer, which evaluated the use of relugolix 40 mg combined with estradiol 1.0 mg and norethindrone acetate 0.5 mg over a 52-week period in women with endometriosis.

The positive results of this expanded study are considered consistent with the efficacy and safety data from the Phase III SPIRIT 1 and SPIRIT 2 trials. The trial data will be submitted to the U.S. Food and Drug Administration (FDA) for a New Drug Application, with the two companies expected to file a regulatory application for the combination therapy in the first half of 2021. If approved, Myovant and Pfizer will also seek to develop the combination therapy of relugolix, estradiol, and norethindrone acetate for the treatment of uterine fibroids and endometriosis.

“In light of the long-term, disruptive impact endometriosis often has on women’s daily lives over many years, patients need noninvasive treatment options suitable for long-term use,” said Dr. Linda Giudice, Distinguished Professor at the Center for Reproductive Sciences, University of California, San Francisco, and a member of the SPIRIT trial steering committee, in a statement. “The one-year clinical data from the SPIRIT Phase 3 extension study provide promising evidence of relugolix’s efficacy, demonstrating that relugolix combination therapy has the potential to significantly and durably alleviate pain in patients with endometriosis while maintaining good tolerability.”

The trial results showed that, during the one-year study period, women receiving relugolix combination therapy achieved clinically meaningful reductions in dysmenorrhea (84.8%) and non-menstrual pelvic pain (73.3%). Over 52 weeks, the mean score on the dysmenorrhea scale among women receiving relugolix combination therapy decreased by 82.8%, dropping substantially from 7.4 (severe pain) to 1.3 (mild pain).

Throughout the study, researchers observed that bone mineral density remained relatively stable in all patients receiving relugolix combination therapy. By Week 24, only a very small number of patients experienced clinically insignificant bone loss with relugolix treatment. Compared with the safety results from the SPIRIT 1 and SPIRIT 2 studies, no new safety signals were identified in the relugolix combination therapy group. Common adverse events (reported in ≥10 participants) included headache, nasopharyngitis, and hot flushes.

This drug is a once-daily, oral gonadotropin-releasing hormone (GnRH) receptor antagonist. Relugolix reduces ovarian estradiol production by blocking GnRH receptors in the pituitary gland; estradiol is a hormone known to stimulate the growth of uterine fibroids and endometriosis. Originally developed by Takeda, the drug was granted exclusive global rights (excluding Japan and other Asian countries) to Myovant (a company formed by Roivant and Takeda) in June 2016. Additionally, the drug can inhibit testicular testosterone production, a hormone that stimulates prostate cancer growth. In December 2020, the drug was officially approved by the FDA, becoming the first oral hormonal therapy for the treatment of advanced prostate cancer in adults.

References:

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