Long-Term Safety of Elagolix With Hormonal Add-Back Therapy in Women With Endometriosis-Associated Pain: 24-Month Results [A86]

INTRODUCTION: Elagolix is an oral GnRH antagonist approved for the treatment of moderate to severe endometriosis-associated pain (EAP) in the US, Canada, and Israel. Hormonal add-back therapy (1 mg estradiol/0.5 mg norethindrone acetate QD) may alleviate the hypoestrogenic effects (including bone mineral density [BMD] loss) associated with elagolix. The long-term safety of elagolix 200mg BID+add-back are currently under investigation in an ongoing phase 3, 48-month (M) study for EAP; this report focuses on open label safety results to 24M. METHODS: Premenopausal women with moderate-to-severe EAP were initially randomized 4:1:2 to receive elagolix 200 mg BID+add-back, elagolix 200 mg BID, or placebo for 12M, followed by open-label elagolix 200 mg BID+add-back for 36M. This 24M analysis assessed long-term safety including BMD. RESULTS: BMD measurements remained stable during the open label treatment period. At 24M, mean percent change from baseline in BMD for patients who initially received elagolix 200 mg BID+add-back (n=123), elagolix 200 mg BID (n=29), or placebo (n=60) was −0.85%, −1.21%, and −0.43% (spine); −0.23%, −0.58%, and −0.20%, (total hip); and −1.05%, −0.98%, and 0.14% (femoral neck). During the open-label period, safety profiles were generally similar across all three original treatment groups at 24M; rates of serious adverse events were generally low (less than 5%) and balanced across groups. CONCLUSION: Elagolix 200 mg BID+add-back therapy for 24M continues to have a favorable safety profile with minimal long-term impact on BMD. Combined with previously reported improvements in dysmenorrhea and non-menstrual pelvic pain, these safety data suggest elagolix 200 mg BID+add-back may provide a longer-term therapeutic option for women with EAP.