INTRODUCTION:: Linzagolix is a new investigational, non-peptide, oral GnRH receptor antagonist being developed to treat endometriosis-associated pain (EAP). The EDELWEISS trial was a Phase 2b, double-blind, randomized, placebo-controlled, multicenter, dose-ranging trial in USA and Europe evaluating once daily oral doses of 50, 75, 100 and 200 mg taken for up to 52 weeks. Subjects randomized to placebo were crossed over to 100 mg after 12 weeks and those randomized to 200 mg were crossed over to 100 mg after 24 weeks. METHODS:: IRB approval was obtained. Participants were women with surgically confirmed endometriosis and moderate to severe EAP. Assessment of EAP included dyspareunia, non-menstrual pelvic pain, dyspareunia and dyschezia symptoms. Quality of life endpoints included the difficulty of doing daily activities, Patient Global Impression of Change/Severity (PGIC/S) and Endometriosis Health Profile-30 (EHP-30). RESULTS:: 327 patients were randomized and treated. Mean age was 32 years and mean BMI was 26. In the treatment groups receiving linzagolix 75 mg and above there were significant improvements compared to placebo in EAP symptoms as well as the EHP-30 domain scores, PGIC and difficulty of doing daily activities at 12 weeks. These improvements were maintained or increased after 52 weeks of treatment. CONCLUSION:: Linzagolix doses of 75 to 200 mg taken once daily for 52 weeks significantly decreased EAP and improved quality of life in women with moderate to severe endometriosis-associated pain.