Two Drugs for Uterine Leiomyomas Show Promise

By Reuters Staff

October 16, 2018

NEW YORK (Reuters Health) - Ulipristal acetate, a selective progesterone receptor modulator, and elagolix, an oral gonadotropin-releasing hormone receptor antagonist, are effective for the treatment of uterine leiomyomas, according to two industry-sponsored randomized controlled trials.

Both studies were published online October 10 and appear in the November issue of Obstetrics & Gynecology.

Uterine leiomyomas are the most common benign gynecologic condition affecting women of childbearing age, with a cumulative incidence by age 50 topping 80% among black women and approaching 70% among white women. Symptomatic uterine leiomyomas are estimated to occur in up to 25% to 50% of women of childbearing age.

Dr. James Liu from Case Western Reserve School of Medicine in Cleveland and colleagues assessed the efficacy and tolerability of Allergan's ulipristal acetate for intermittent treatment of symptomatic uterine leiomyomas in a phase 3 study.

They randomly allocated 432 premenopausal women to 5 mg or 10 mg ulipristal once daily or placebo in two 12-week treatment courses separated by a drug-free interval of two menses.

"For the coprimary end points of rates of and time to amenorrhea (with spotting permitted) during the first 12-week course of treatment, each ulipristal dose was superior to placebo (P<0.001)," the investigators report in their paper.

"Ulipristal treatment was shown to induce amenorrhea rapidly, reduce leiomyoma volume, and improve health-related quality of life, including physical and social activities. The efficacy of both doses of ulipristal was maintained during the second course of treatment after an off-treatment interval of two menses," they say.

Ulipristal was generally well tolerated. Most side effects were mild or moderate and they occurred less often during the second treatment course. The most common adverse event that occurred more frequently in ulipristal-treated patients was hot flush.

Dr. Liu and colleagues conclude, "Given the clinical profile of 5 mg and 10 mg ulipristal observed in this and other trials, intermittent 12-week courses of treatment with ulipristal, followed by off-treatment intervals, may be considered a preferred option for the medical management of symptomatic uterine leiomyomas, particularly for women desiring uterine-sparing therapy."

Dr. Bruce Carr from the University of Texas Southwestern Medical School in Dallas and colleagues evaluated AbbVie's elagolix alone (300 mg twice daily or 600 mg daily) or with add-back therapy (0.5 mg estradiol/0.1 norethindrone acetate or 1.0 mg estradiol/0.5 mg norethindrone acetate) in women with heavy menstrual bleeding (>80 mL per month) associated with uterine leiomyomas. This was a phase 2b, double-blind, randomized, placebo-controlled parallel-group study involving 567 women.

"Elagolix treatment with and without add-back therapy showed superiority to placebo in significantly reducing menstrual bleeding, increasing hemoglobin concentration, and reducing leiomyoma and uterine volumes in women with heavy menstrual bleeding associated with uterine leiomyomas," the investigators report. "These results were associated with improvements in quality of life and confirmed the phase 2a study efficacy results for the 600-mg total daily dose of elagolix in improving heavy menstrual bleeding with statistical comparison with placebo for two dosing regimens."

"Elagolix with add-back therapy showed an acceptable safety profile in women with heavy menstrual bleeding associated with uterine leiomyomas," they write, adding, "Hormone add-back therapy attenuated hypoestrogenic effects of elagolix on bone mineral density while maintaining the efficacy on reducing heaving menstrual bleeding in women with uterine leiomyomas."

Allergan supported the ulipristal study. Dr. Liu and several co-authors have disclosed financial relationships with the company. AbbVie funded the elagolix study. Dr. Carr and several co-authors have ties to the company.


Obstet Gynecol 2018.