What is the clinical efficacy of Myfembree in treating uterine fibroids?

Also called Ryeqo, relugolix/estradiol/norethindrone acetate has demonstrated good efficacy and safety in clinical trials, providing a new non-invasive treatment option for patients with uterine fibroids.

Myfembree is the first once-daily medication approved by the U.S. FDA for the treatment of uterine fibroid-related menorrhagia (HMB) in premenopausal women for up to 24 months.

Myfembree

Myfembree (TAK-385) was developed by Takeda and has been approved for marketing for the treatment of endometriosis, uterine fibroids, prostate cancer, etc.

Myfembree is a non-cutaneous GnRH receptor antagonist that competitively binds to pituitary GnRH receptors, thereby reducing the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), resulting in lower serum concentrations of the ovarian sex hormones estradiol and progesterone, and reducing bleeding associated with uterine fibroids and pain associated with endometriosis.

Estradiol works by binding to nuclear receptors expressed in estrogen-responsive tissues, and progestins such as norethindrone work by binding to nuclear receptors expressed in progesterone-responsive tissues. As an ingredient in Myfembree, norethindrone protects the uterus from the potentially adverse endometrial effects of unopposed estrogens.

Clinical application of Myfembree in treating uterine fibroids

According to efficacy and safety data from a phase 3 clinical trial, 72.1% of women in the Myfembree treatment group achieved response criteria at week 24, while only 16.8% of women in the placebo group achieved response criteria. Relative to baseline, menstrual blood loss (MBL) in the treatment groups was reduced by 82% and 84.3%, respectively. Relief of symptoms means that the menstrual blood loss is less than 80ml in the last 35 days of treatment and the menstrual blood loss is reduced by more than 50% compared with the beginning.

In a double-blind, randomized, multicenter study, 1,176 healthy postmenopausal women aged 45 years or older with no evidence of endometrial abnormalities received 12 months of treatment with a continuous combination of unopposed 17β-estradiol (E2), 1 mg, or E2, 1 mg, and norethindrone acetate 0.1 mg, 0.25 mg, or 0.5 mg. Endometrial histology was assessed at the end of the treatment period.

Compared with unopposed 17β-estradiol (E2) 1 mg, the continuous combination E2-norethindrone acetate regimen significantly reduced the incidence of endometrial hyperplasia at 12 months. Endometrial hyperplasia occurred in 14.6% of women treated with unopposed 17β-estradiol (E2) 1 mg, and this rate dropped to less than 1% in all continuous combination therapy groups.

The incidence was 0.8% in patients receiving 0.1 mg of estradiol-norethindrone acetate. 0.4% among those receiving 0.25 mg and 0.5 mg.

Continuous norethindrone acetate as low as 0.1 mg in combination with 17β-estradiol (E2) 1 mg effectively eliminates the risk of endometrial hyperplasia associated with unopposed 17β-estradiol (E2) 1 mg, at least during the first year of treatment.

References:

Kurman RJ, Félix JC, Archer DF, Nanavati N, Arce J, Moyer DL. Norethindrone acetate and estradiol-induced endometrial hyperplasia. Obstet Gynecol. 2000 Sep;96(3):373-9. doi: 10.1016/s0029-7844(00)00944-3. PMID: 10960628.

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