AbbVie in cooperation with Neurocrine Biosciences, announced that the Phase 3 ELARIS UF-I study (M12-815) of elagolix met its primary endpoint. Results from the first of two pivotal Phase 3 studies demonstrated at month six that elagolix, in combination with low-dose hormone (add-back) therapy, reduced heavy menstrual bleeding with 68.5 percent (p<0.001) of women with uterine fibroids achieving clinical response compared to placebo (8.7 percent), as measured by the alkaline hematin method. Clinical response was defined as menstrual blood loss volume of less than 80 mL during month six and a 50 percent or greater reduction in menstrual blood loss volume from baseline to month six. The study also met all ranked secondary endpoints (p<0.001) at month six.
Uterine fibroids are the most common type of abnormal growth in a woman's pelvis and can affect up to 80 percent of women by age 50. Fibroids can be asymptomatic, but in approximately 25 percent 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.
"Current non-surgical treatments are limited and women suffering from uterine fibroids need more therapeutic options," said Dawn Carlson, M.D., M.P.H., vice president, general medicine development. "The results from this study represent a significant advancement in the development of elagolix and demonstrate our continued commitment to address serious disease."
Hypoestrogenic effects, such as hot flush and reduction in bone mineral density, from elagolix treatment were observed in the study. In addition, the overall safety profile for elagolix was consistent with what was 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 currently 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.
Uterine fibroids (also called leiomyomas or myomas) are non-cancerous, hormonally-responsive muscle tissue tumors of the uterus. Fibroids are the most common type of abnormal growth in a woman's pelvis and can affect about 20-80 percent of women by age 50. Fibroids can range in size, shape, number and location. Fibroids can be asymptomatic, but in some women, fibroids can cause symptoms such as heavy menstrual bleeding, painful periods, vaginal bleeding at times other than menstruation, anemia, pain in the abdomen or lower back, pain during sex, difficulty urinating or frequent urination, constipation, rectal pain or difficulty getting pregnant. Treatment options for uterine fibroids include surgery (hysterectomy, myomectomy), hysteroscopy, endometrial ablation, uterine artery embolization, magnetic resonance imaging-guided ultrasound and medical management with treatments such as oral contraceptives, progestins, selective progesterone receptor modulators, and GnRH agonists, some of which are not specifically indicated for the treatment of uterine fibroids.
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, age 18–51 years old, with a diagnosis of uterine fibroids documented by a pelvic transvaginal and transabdominal ultrasound (TAU, TVU). 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. Clinical response was defined as menstrual blood loss volume of less than 80 mL during month six and a 50 percent or greater reduction in menstrual blood loss volume from baseline to month six. 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 (LH) and follicle-stimulating hormone (FSH) secretion, leading to reduced ovarian production of the ovarian sex hormones, estradiol and progesterone, while on therapy. Elagolix is currently being investigated in diseases that are mediated by ovarian sex hormones, such as uterine fibroids and endometriosis. To date, elagolix has been studied in over 40 clinical studies, totaling more than 3,700 subjects. Phase 3 studies of elagolix for the management of uterine fibroids are ongoing.