THE EFFECT OF ELAGOLIX ON THE ENDOMETRIUM: SAFETY RESULTS FROM TWO RANDOMIZED, PLACEBO-CONTROLLED STUDIES IN WOMEN WITH ENDOMETRIOSIS-ASSOCIATED PAIN.

To evaluate the effect of elagolix, an oral, non-peptide gonadotropin-releasing hormone antagonist, on endometrial morphology and thickness after treatment for 6 months in women with moderate/severe endometriosis-associated pain (EAP). These were two similar, double-blind, randomized, placebo-controlled, multicenter, 6 months, phase 3 studies (Studies 1 [North America] and 2 [global]) evaluating two doses of elagolix (150mg once daily [QD; partial estrogen suppression1] and 200mg twice daily [BID; near full estrogen suppression1]) compared to placebo. Study participants (Study 1, n=871; 2, n=815) were premenopausal, 18-49 year-old women with surgically diagnosed endometriosis. Endometrial biopsies were performed at baseline and month 6 in Study 1, and not in Study 2. Endometrial thickness was measured via trans-vaginal ultrasound at baseline (day 2-8 of menstrual cycle) and at month 6 in both studies. Based on the endometrial biopsies of 867 participants at baseline and 644 at treatment month 6 in Study 1, there was a dose-dependent reduction in proliferative and secretory patterns, an increase in quiescent/minimally stimulated endometrial patterns, and no findings of endometrial hyperplasia after 6 months of treatment with elagolix (Table). At baseline in Study 1, the mean endometrial thickness was 6.8 mm for placebo and 6.5 mm in each elagolix group; the mean (SD) change from baseline to month 6 was 0.6 (3.4) mm at 150 mg QD and -1.4 (3.2) mm at 200 mg BID, which was statistically significant at 200 mg BID (p<0.001) compared to placebo (mean [SD] change from baseline to month 6=1.0 [3.3] mm). At baseline in Study 2, the mean endometrial thickness was 6.3 mm for placebo and 6.5 mm for elagolix 150 mg QD and 6.4 mm for elagolix 200 mg BID; the mean (SD) change from baseline to month 6 was 0.4 (3.7) mm at 150 mg QD and -0.8 (3.5) mm at 200 mg BID, which was statistically significant at 200 mg BID (p<0.001) compared to placebo (mean [SD] change from baseline to month 6=1.0 [3.3] mm). There were no adverse endometrial findings in these studies. In women with EAP, elagolix treatment suppressed endometrial proliferation in a dose-dependent manner after 6 months of treatment with no evidence of endometrial hyperplasia, consistent with its mechanism of action.Tabled 1Study 1 Endometrial Biopsy Results at Baseline and Month 6STUDY 1, n (%)Placebo, N=374Elagolix 150 mg QD, N=249Elagolix 200 mg BID, N=248Endometrium:BaselineMonth 6BaselineMonth 6BaselineMonth 6Normal quiescent/minimally stimulated10 (2.7)6 (1.6)8 (3.2)26 (10.4)4 (1.6)107 (43.1)Normal secretory156 (42)141 (38)98 (39)51 (21)93 (38)12 (2.8)Proliferative200 (54)129 (35)131 (53)105 (42)143 (58)46 (19)Hyperplasia001 (0.4)000Reactive/inflammatory0001 (0.4)00Insufficient tissue3 (0.8)5 (1.3)1 (0.4)4 (1.6)5 (2.0)15 (6.0)QD = once daily; BID = twice daily. Open table in a new tab