Elagolix (AbbVie) and low-dose hormone therapy reduced heavy menstrual bleeding among women with uterine fibroids in the phase 3 ELARIS UF-I study, with 68.5% achieving a clinical response compared with placebo (8.7%).
Clinical response, measured by the alkaline hematin method, was defined as menstrual blood loss volume of less than 80 mL during month 6 and a 50% or greater reduction in menstrual blood loss volume from baseline to month 6. The study met its primary endpoint and all ranked secondary endpoints (P < 0.001) at month 6 in the first of two pivotal phase 3 studies.
Uterine fibroids are the most common type of abnormal growth in a woman's pelvis and can affect up to 80% of women by age 50. Fibroids can be asymptomatic, but in approximately 25% of women, fibroids can cause symptoms, such as heavy menstrual bleeding, painful periods, vaginal bleeding at times other than menstruation, and anemia. African-American women are more likely to experience fibroids and do so at a younger age.
Hypoestrogenic effects, such as hot flush and reduction in bone mineral density, from elagolix treatment were observed in the study. The overall safety profile for elagolix was consistent with that observed in phase 2 studies in uterine fibroids. Data from the phase 3 study will support regulatory submissions for elagolix and will be presented at an upcoming medical conference. Safety data, including most common adverse events, are being analyzed.
The topline results are from a six-month primary analysis. Women in the study will continue in either post-treatment follow-up or a blinded six-month extension study.
ELARIS UF-I is the first of two replicate, pivotal, six-month phase 3 studies evaluating the safety, tolerability, and efficacy of elagolix alone and in combination with low-dose hormone (add-back) therapy (estradiol/norethindrone acetate) in women with uterine fibroids. Study participants were premenopausal women, 18–51 years of age, with a diagnosis of uterine fibroids documented by a pelvic transvaginal and transabdominal ultrasound. The primary endpoint assessed the reduction in heavy menstrual bleeding compared to placebo as measured by the alkaline hematin method, an objective measurement of total menstrual blood loss based on quantitation of menstrual blood collected on sanitary products. The ranked secondary endpoints included measures of bleeding, bleeding suppression, and hemoglobin changes. The study was conducted at approximately 90 sites in the United States and Canada.
Elagolix, a gonadotropin-releasing hormone (GnRH) receptor antagonist, is an orally administered, short-acting molecule that blocks endogenous GnRH signaling by binding competitively to GnRH receptors in the pituitary gland. Administration results in rapidly reversible, dose-dependent inhibition of luteinizing hormone and follicle-stimulating hormone secretion, leading to reduced ovarian production of the ovarian sex hormones, estradiol and progesterone, while on therapy.
Source: AbbVie; February 21, 2018.