Elagolix, an oral gonadotropin-releasing hormone antagonist, for the management of endometriosis-associated pain: safety and efficacy results from two double-blind, randomized, placebo-controlled studies

Abstract

OBJECTIVE: To evaluate the safety and efficacy of elagolix, an oral, nonpeptide gonadotropin-releasing hormone antagonist, as compared to placebo in the management of moderate/severe endometriosis-associated pain (EAP). DESIGN: These were two similar, double-blind, randomized, placebocontrolled, multicenter, 6-month, phase 3 studies (Studies 1 [North America] and 2 [global]) evaluating two doses of elagolix (150mg once daily [QD] and 200mg twice daily [BID]). Each study has an ongoing 6-month extension study. MATERIALSANDMETHODS: Participants were 18-49 year-old women with surgically diagnosed endometriosis within prior 10 years and moderate/ severe EAP. The co-primary efficacy endpoints were the proportion of responders (controlled for rescue analgesic use) at month 3 based on daily dysmenorrhea (DYS) and non-menstrual pelvic pain (NMPP) scores recorded in an electronic diary. The clinically meaningful response for DYS and NMPP was determined with a receiver operating characteristics analysis using the Patient Global Impression of Change (PGIC, ''much'' or ''very much'' improved) as the anchor. The proportion of DYS and NMPP responders at month 6 was a secondary endpoint. Safety assessments included adverse events (AE), clinical laboratory tests, and changes in bone mineral density and endometrium. RESULTS: In Studies 1 and 2 respectively, 871 and 815 participants were randomized and treated; 653 (75%) and 631 (77%) completed. Compared to placebo, each dose of elagolix resulted in a significantly greater proportion of responders for DYS and NMPP, at months 3 (Table) and 6. Hot flush (mostly mild/moderate), headache and nausea were the most common AEs for elagolix- treated participants (Table). A dose-dependent increase in serum lipids and decrease in BMD were observed with elagolix treatment. There were no adverse endometrial findings. CONCLUSIONS: In women with EAP, elagolix showed dose-dependent superiority compared to placebo in reducing DYS and NMPP over 6 months in two large studies. The safety/tolerability profile was consistent with dosedependent hypoestrogenic effects.