Long-term effect of elagolix on bone mineral density: results from two phase 3 extension studies in women with endometriosis-associated pain

Abstract

To evaluate the long-term effect of elagolix, an oral, non-peptide gonadotropin-releasing hormone antagonist, on bone mineral density (BMD) in women with moderate/severe endometriosis-associated pain. Elaris EM-III and Elaris EM-IV were two extension studies of the 6-month (M) pivotal, phase 3 studies, which evaluated two elagolix doses (150 mg once daily [QD] and 200 mg twice daily [BID]) for an additional 6M (overall treatment period of 12M) and up to 12M post-treatment period. Presented data are from women who received elagolix in both the pivotal and extension studies. Study participants (Elaris EM-III, n=287; Elaris EM-IV, n=282) were premenopausal, 18-49 year-old women with endometriosis and a baseline BMD Z-score higher than -1.5. Lumbar spine BMD was measured by dual energy X-ray absorptiometry. A central reader evaluated images and numeric results, blinded to treatment groups. Baseline was prior to dosing in the previous pivotal studies. Due to enrollment timing in the extension studies, some women received >12M of treatment. Post-treatment analyses of BMD recovery are ongoing. Following 12M of treatment in Elaris EM-III and EM-IV, the mean BMD Z-score of the lumbar spine was 0.5 and 0.3 in the 150mg QD group respectively, and 0.2 and -0.04 in the 200mg BID group (Table) which is within the normal range of -2.0 to +2.0 (Ref 1). Following 12M of treatment in Elaris EM-III and EM-IV, there were 0.9% and 0.8% in the 150mg QD group respectively, and 13% and 11% in the 200mg BID group with a decrease in mean BMD ≥8%. In women with endometriosis-associated pain, long-term elagolix treatment was associated with a decrease in lumbar spine BMD, which was greater with 200mg BID.Tabled 1Changes in Lumbar Spine Bone Mineral Density in Women with Endometriosis-associated PainLumbar Spine Bone Mineral DensityElaris EM-III, Elagolix 150 mg QD, N=114Elaris EM-III, Elagolix 200 mg BID, N=108Elaris EM-IV, Elagolix 150 mg QD, N=122Elaris EM-IV, Elagolix 200 mg BID, N=111Mean Z-score at BL0.6a0.5c0.4e0.4fMean Z-score, M12 (extension M6)0.50.20.3-0.04Mean density at BL in gms/cm21.2b1.2d1.2e1.2fMean (95% CI) percentage change from BL to M12 (extension M6)-0.6 (-1.2, -0.04)-3.6 (-4.2, -3.0)-1.1 (-1.7, -0.6)-3.9 (-4.5, -3.3)No change or increase, n (%)49 (43%)16 (15%)43 (35%)17 (15%)Decrease ≤ 3%, n (%)46 (40%)30 (28%)49 (40%)26 (23%)Decrease >3, ≤ 5%, n (%)15 (13%)20 (19%)25 (20%)22 (20%)Decrease >5 , < 8%, n (%)3 (2.6%)28 (26%)4 (3.3%)33 (30%)Decrease ≥ 8% , n (%)1 (0.9%)14 (13%)1 (0.8%)13 (12%)BL = baseline; M=month. Data are preliminary; the presentation will include final data. (a) N=116; (b) N=117; (c) N=115; (d) N= 120; (e) N=127; (f) N=121 Open table in a new tab