The Food and Drug Administration (FDA) has expanded the approval of Myfembree® (relugolix, estradiol, and norethindrone acetate) to include management of moderate to severe pain associated with endometriosis.

The approval was based on data from the phase 3 SPIRIT program, which included the 24-week, double-blind, placebo-controlled SPIRIT 1 (ClinicalTrials.gov Identifier: NCT03204318) and SPIRIT 2 (ClinicalTrials.gov Identifier: NCT03204331) studies, as well as the first 28 weeks of an open-label extension study (ClinicalTrials.gov Identifier: NCT03654274). The SPIRIT 1 and 2 trials evaluated the efficacy and safety of Myfembree in more than 1200 women with pain associated with endometriosis.

Patients were randomly assigned 1:1:1 to receive relugolix 40mg once daily plus estradiol 1mg and norethindrone 0.5mg (equivalent to 1 tablet of Myfembree) for 24 weeks, relugolix 40mg once daily monotherapy for 12 weeks followed by Myfembree for an additional 12 weeks, or placebo for 24 weeks. The primary outcome measures were the percentage of patients who met the dysmenorrhea and nonmenstrual 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: 75.1% vs 30.5%; P <.0001) and nonmenstrual pelvic pain (SPIRIT 1: 58.5% vs 39.6%; SPIRIT 2: 65.9% vs 42.5%; P <.0001). Both studies also met key secondary endpoints including reduction in dyspareunia and improvement on the Endometriosis Health Profile-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 treatment with Myfembree resulted in clinically meaningful reductions in dysmenorrhea and nonmenstrual pelvic pain with mean bone mineral density loss of less than 1% from baseline at 1 year. 

“The data from the SPIRIT studies showed the clinical benefit that relugolix combination therapy can have on moderate to severe pain associated with endometriosis and how it can impact patients,” said Linda Giudice, MD, PhD, Distinguished Professor at the University of California, San Francisco (UCSF), and Chair, SPIRIT Program Steering Committee. “This newly approved option for patients with pain from endometriosis offers the convenience of one pill taken once daily with a mean change in bone mineral density of <1% that did not appear to worsen at 12 months of treatment; however, monitoring is recommended.”

Myfembree is supplied as a film-coated, fixed-dose combination tablet containing relugolix 40mg, estradiol 1mg, and norethindrone acetate 0.5mg in a 28-count bottle. Prior to initiating treatment, pregnancy should be excluded and hormonal contraceptives should be discontinued.

References

  1. Myovant Sciences and Pfizer receive US FDA approval of Myfembree®, a once-daily treatment for the management of moderate to severe pain associated with endometriosis. News release. Myovant Sciences, Inc. Accessed August 8, 2022. https://www.globenewswire.com/news-release/2022/08/06/2493463/0/en/Myovant-Sciences-and-Pfizer-Receive-U-S-FDA-Approval-of-MYFEMBREE-a-Once-Daily-Treatment-for-the-Management-of-Moderate-to-Severe-Pain-Associated-With-Endometriosis.html
  2. Myfembree. Package insert. Myovant Sciences, Inc.; 2022. Accessed August 8, 2022. https://www.myovant.com/wp-content/uploads/2022/08/Approved-MYFEMBREE-PI-and-PPI_05August2022.pdf