Phase 3 Trial Results: Efficacy and Safety of Elagolix in a Subset of Women with Uterine Fibroids and Adenomyosis

Study Objective Adenomyosis is a benign lesion within the myometrium associated with heavy menstrual bleeding (HMB) and dysmenorrhea, and commonly co-exists with uterine fibroids (UF). This analysis evaluated the efficacy and safety of elagolix, an oral, gonadotropin-releasing hormone receptor antagonist, with add-back therapy in a subset of women with UF, HMB and co-existing adenomyosis. Design Data were pooled from two 6-month, randomized, double-blind, placebo-controlled phase 3 studies, Elaris UF-1 and UF-2. Setting Outpatient in clinic/office Patients or Participants Premenopausal women (18-51 years) with HMB (>80mL menstrual blood loss [MBL]/cycle) associated with UF and co-existing adenomyosis diagnosed by ultrasound and/or MRI at baseline (BL). Interventions Women were randomized 1:1:2 to placebo, elagolix 300mg twice daily (BID), or elagolix 300mg BID with 1mg estradiol/0.5mg norethindrone acetate (E2/NETA) once daily. Measurements and Main Results The primary endpoint was the proportion of women with <80mL MBL during the final month and ≥50% reduction in MBL from BL to the final month. MBL and the diagnosis of HMB was assessed with the alkaline hematin method. Adverse events (AEs) were monitored. Of 790 women treated, 16% had ultrasound and/or MRI diagnosed adenomyosis at BL. Pooled data demonstrated that the proportion of responders for the primary endpoint was significantly greater (P<0.001) for elagolix+E2/NETA [76.8% (95% CI, 65.84, 87.82)] compared to placebo [12.1% (95% CI, 0.97, 23.150)]. AEs reported in the adenomyosis subset included hot flushes, night sweats, headache, and nausea. Conclusion In women with HMB associated with UF and co-existing adenomyosis at BL, elagolix +E2/NETA significantly reduced MBL versus placebo similar to the all-subject group. AEs reported in this group were similar to the all-subject group. These data suggest that further studies investigating the effect of elagolix in women with HMB associated with UF and adenomyosis may be warranted. Adenomyosis is a benign lesion within the myometrium associated with heavy menstrual bleeding (HMB) and dysmenorrhea, and commonly co-exists with uterine fibroids (UF). This analysis evaluated the efficacy and safety of elagolix, an oral, gonadotropin-releasing hormone receptor antagonist, with add-back therapy in a subset of women with UF, HMB and co-existing adenomyosis. Data were pooled from two 6-month, randomized, double-blind, placebo-controlled phase 3 studies, Elaris UF-1 and UF-2. Outpatient in clinic/office Premenopausal women (18-51 years) with HMB (>80mL menstrual blood loss [MBL]/cycle) associated with UF and co-existing adenomyosis diagnosed by ultrasound and/or MRI at baseline (BL). Women were randomized 1:1:2 to placebo, elagolix 300mg twice daily (BID), or elagolix 300mg BID with 1mg estradiol/0.5mg norethindrone acetate (E2/NETA) once daily. The primary endpoint was the proportion of women with <80mL MBL during the final month and ≥50% reduction in MBL from BL to the final month. MBL and the diagnosis of HMB was assessed with the alkaline hematin method. Adverse events (AEs) were monitored. Of 790 women treated, 16% had ultrasound and/or MRI diagnosed adenomyosis at BL. Pooled data demonstrated that the proportion of responders for the primary endpoint was significantly greater (P<0.001) for elagolix+E2/NETA [76.8% (95% CI, 65.84, 87.82)] compared to placebo [12.1% (95% CI, 0.97, 23.150)]. AEs reported in the adenomyosis subset included hot flushes, night sweats, headache, and nausea. In women with HMB associated with UF and co-existing adenomyosis at BL, elagolix +E2/NETA significantly reduced MBL versus placebo similar to the all-subject group. AEs reported in this group were similar to the all-subject group. These data suggest that further studies investigating the effect of elagolix in women with HMB associated with UF and adenomyosis may be warranted.