OBJECTIVE: To evaluate the efficacy and safety of elagolix, an oral, nonpeptide 
gonadotropin-releasing hormone antagonist, over 12 months in women with 
endometriosis-associated pain.
METHODS: Elaris Endometriosis (EM)-III and -IV were extension studies that 
evaluated an additional 6 months of treatment after two 6-month, double-blind, 
placebo-controlled phase 3 trials (12 continuous treatment months) with two 
elagolix doses (150 mg once daily and 200 mg twice daily). Coprimary efficacy 
endpoints were the proportion of responders (clinically meaningful pain 
reduction and stable or decreased rescue analgesic use) based on average monthly 
dysmenorrhea and nonmenstrual pelvic pain scores. Safety assessments included 
adverse events, clinical laboratory tests, and endometrial and bone mineral 
density assessments. The power of Elaris EM-III and -IV was based on the 
comparison to placebo in Elaris EM-I and -II with an expected 25% dropout rate.
RESULTS: Between December 28, 2012, and October 31, 2014 (Elaris EM-III), and 
between May 27, 2014, and January 6, 2016 (Elaris EM-IV), 569 participants were 
enrolled. After 12 months of treatment, Elaris EM-III responder rates for 
dysmenorrhea were 52.1% at 150 mg once daily (Elaris EM-IV 550.8%) and 78.2% at 
200 mg twice daily (Elaris EMIV 575.9%). Elaris EM-III nonmenstrual pelvic pain 
responder rates were 67.5% at 150 mg once daily (Elaris EM-IV 566.4%) and 69.1% 
at 200 mg twice daily (Elaris EM-IV 567.2%).”After 12 months of treatment, 
Elaris EM-III dyspareunia responder rates were 45.2% at 150 mg once daily 
(Elaris EM-IV=45.9%) and 60.0% at 200 mg twice daily (Elaris EM-IV=58.1%). Hot 
flush was the most common adverse event. Decreases from baseline in bone mineral 
density and increases from baseline in lipids were observed after 12 months of 
treatment. There were no adverse endometrial findings.
CONCLUSION: Long-term elagolix treatment provided sustained reductions in 
dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia. The safety was 
consistent with reduced estrogen levels and no new safety concerns were 
associated with long-term elagolix use.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01760954 and NCT02143713.