Up to 80% of women who are of reproductive age have uterine fibroids that cause heavy and prolonged bleeding.1 Additional concerns include infertility and pain, says James Simon, MD, Clinical Professor at George Washington University in Washington, DC. Black women are more likely than white women to undergo hysterectomy for uterine fibroids. They also are more likely to experience severe or very severe symptoms from fibroids and report that these symptoms interfere with physical activities, relationships, and work.2
Current medical treatments include on- and off-label use of oral contraceptives, gonadotropin-releasing hormone (GnRH) receptor agonists, and progestins. Data on investigational oral GnRH antagonists and oral selective progesterone-receptor modulators (SPRMs) were presented at the 2017 Annual Clinical and Scientific Meeting of the American College of Obstetricians and Gynecologists.
Details of VENUS I
In the phase 3, randomized, controlled VENUS I trial, investigators assessed the efficacy and safety of ulipristal acetate (UPA), an SPRM, by race and body mass index (BMI) in premenopausal women (aged 18 to 50) with symptomatic uterine fibroids.1
Simon and colleagues randomly assigned participants to UPA 5 mg, UPA 10 mg, or placebo once daily for 12 weeks, followed by a 12-week treatment-free follow-up period. UPA, at 5 and 10 mg, was significantly more efficacious than placebo in rate of and time to amenorrhea (P<.0001). The superiority was observed regardless of race and BMI. In addition, women taking UPA versus placebo reported significantly less impact on activities due to uterine fibroids. The study authors concluded that “UPA treatment provides effective control of bleeding and improvement in physical and social activities for women with symptomatic uterine fibroids, regardless of race and BMI.”1
Establishing the ideal treatment period for UPA to avoid progesterone-associated endometrial changes (in this study it was 12 weeks of once-daily therapy) is a current goal, said Simon.
Details of elagolix phase 2b study
Simon also presented data on another investigational drug, elagolix, an orally administered GnRH antagonist, which has an inhibiting effect on luteinizing hormone and follicle-stimulating hormone secretion. This in turn reduces production of estradiol and progesterone. Elagolix also is being studied for the treatment of endometriosis.3
In the uterine fibroids study, a 24-week, multicenter, double-blind, randomized controlled, parallel group trial, 567 premenopausal women aged 18 to 51 with heavy menstrual bleeding of >80 mL of blood loss were assigned to placebo or elagolix 300 mg twice per day or 600 mg once per day alone or in combination with add-back therapy (with estradiol/norethindrone acetate) to prevent bone loss and menopausal symptoms.4
Compared with placebo, women treated with elagolix with or without add-back therapy had significant reductions from baseline in mean menstrual blood loss. Women treated with elagolix also had significant increases in hemoglobin concentration from baseline to month 6 compared with placebo.4
Adverse effects were similar to menopause symptoms: bone loss, hot flashes, night sweats, headaches, and disturbed sleep, said Simon. With the add-back treatments, adverse effects were mitigated in a dose-dependent fashion, he pointed out, and were most likely tolerable compared with the heavy bleeding experienced by women at the start of the study.