The Food and Drug Administration (FDA) has approved Myfembree® (relugolix, estradiol, and norethindrone acetate) for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women.
Myfembree is a combination of relugolix, a gonadotropin-releasing hormone receptor antagonist, estradiol, an estrogen, and norethindrone acetate, a progestin. The approval was based on 2 randomized, double-blind, placebo-controlled studies: LIBERTY 1 (ClinicalTrials.gov Identifier: NCT03049735) and LIBERTY 2 (ClinicalTrials.gov Identifier: NCT03103087).
In both studies, premenopausal women with heavy menstrual bleeding associated with uterine fibroids (N=768) were randomly assigned 1:1:1 to receive a relugolix combination therapy (equivalent to 1 tablet of Myfembree) for 24 weeks, placebo for 24 weeks, or relugolix monotherapy for 12 weeks followed by Myfembree for 12 weeks. The primary endpoint was the proportion of women who achieved menstrual blood loss volume of less than 80mL and at least a 50% reduction from baseline in menstrual blood loss volume during the last 35 days of the 24-week treatment period (responder criteria).
Findings showed that in both studies, a statistically higher proportion of women treated with Myfembree achieved the primary endpoint compared with placebo (72.1% vs 16.8% in LIBERTY 1 and 71.2% vs 14.7% in LIBERTY 2; both P <.0001). Additionally, the mean reduction in menstrual blood volume from baseline to week 24 in the Myfembree group was 82.0% in LIBERTY 1 and 84.3% in LIBERTY 2, compared with 19.1% and 15.1% for placebo, respectively (both P <.0001).
The most commonly reported adverse reactions included hot flush, hyperhidrosis or night sweats, uterine bleeding, alopecia, and decreased libido. The Myfembree prescribing information includes a Boxed Warning regarding the risk of thrombotic or thromboembolic disorders, especially in women at increased risk for these events. Myfembree may cause a decrease in bone mineral density in some patients; use should be limited to 24 months due to the risk of continued bone loss which may not be reversible.
Contraindications to treatment include high risk of arterial, venous thrombotic, or thromboembolic disorder, pregnancy, known osteoporosis, current or history of breast cancer or other hormone-sensitive malignancies, known hepatic impairment or disease, and undiagnosed abnormal uterine bleeding.
Myfembree is supplied as a film-coated, fixed-dose combination tablet containing relugolix 40mg, estradiol 1mg, and norethindrone acetate 0.5mg and is administered as a once-daily therapy. Prior to initiating treatment, pregnancy should be excluded and hormonal contraceptives should be discontinued.
The product is expected to be available in June 2021.
- Myovant Sciences and Pfizer receive FDA approval for Myfembree®, the first once-daily treatment for heavy menstrual bleeding associated with uterine fibroids. [press release]. Basel, Switzerland and New York, NY: Myovant Sciences and Pfizer Inc.; May 26, 2021.
- Myfembree [package insert]. Basel, Switzerland and New York, NY: Myovant Sciences and Pfizer Inc.; 2021.