Long-term safety and efficacy of elagolix, an oral, non-peptide GnRH antagonist for the management of endometriosis-associated pain, was evaluated in two 6-month (M) extension studies (Elaris EM-III and IV) of the pivotal, 6M, phase 3 studies (12M-overall treatment with 150 mg once daily [QD] or 200 mg twice daily [BID]).METHODS:
Women with moderate/severe endometriosis-associated pain, randomized to receive elagolix in the pivotal studies, continued treatment during the extension studies (treated: Elaris EM-III, n=287; Elaris EM-IV, n=282). Baseline was before dosing in pivotal studies. Dysmenorrhea (DYS), non-menstrual pelvic pain (NMPP), and dyspareunia (DYSP) scores were recorded in a daily electronic-diary. Adverse events (AE), bone mineral density (BMD), and endometrium were assessed.RESULTS:
DYS, NMPP and DYSP scores across dose groups were significantly decreased compared to placebo at M6 in the pivotal studies (P<.05; exception-DYSP 150 mg), and improvements in scores were maintained after 12M of treatment in Elaris EM-III (Extension-M6 mean percent change from baseline: DYS, 150 mg QD=−49%, 95% CI [−57,−41], 200 mg BID=−82%, 95% CI [−88,−76], NMPP, 150 mg QD=−49, 95% CI [−57,−41], 200 mg BID=−57%, 95% CI [−64,−49]; DYSP, 150 mg QD=−31%, 95% CI [−46,−16], 200 mg BID=−42%, 95% CI [−58,−25]). Hot flush was the most common AE over 12M of treatment (150 mg QD=29.5%; 200 mg BID=52.2%). At extension M6, there was a dose-dependent decrease in BMD from baseline, while mean lumbar spine BMD Z-score was within normal range (−2.0–+2.0). Mean change in endometrial thickness ranged 0.6 to −0.8 mm across doses. Elaris EM-IV results were generally similar.CONCLUSION:
In women with endometriosis-associated pain, long-term elagolix treatment was associated with reductions in DYS, NMPP, and DYSP. No new safety concerns were identified with long-term elagolix use.