Clinical Trials

Elagolix: An Investigational Treatment for Endometriosis

The endometriosis Phase III program is assessing two separate doses of elagolix (150mg once daily and 200mg twice daily) over an initial 24-week treatment period. The initial randomized, parallel, double-blind, placebo-controlled pivotal trial (Violet PETAL) enrolled  872 women in approximately 160 clinical sites throughout the United States, Canada and Puerto Rico. The co-primary endpoints were a comparison of the daily non-menstrual pelvic pain and daily dysmenorrhea scores during the third month of treatment to the respective daily baseline scores utilizing a responder analysis. Maintenance of response at month six was also assessed utilizing the same daily scales.

On January 8, 2015, AbbVie released the top-line results of the initial six months of placebo controlled dosing of the Violet PETAL study. After six months of continuous treatment, both doses of elagolix (150 mg once daily and 200 mg twice daily) met the study’s co-primary endpoints (p<0.001) of reducing scores of non-menstrual pelvic pain and dysmenorrhea associated with endometriosis at month three, as well as at month six.

The observed safety profile of elagolix in the Violet PETAL study was consistent with observations from prior studies. Among the most common adverse events were hot flash, headache, nausea and fatigue.  While most adverse events were similar across treatment groups, some, such as hot flash and bone mineral density loss were dose-dependent. Overall discontinuation rates were similar across treatment groups and discontinuations specifically due to adverse events were 5.9%, 6.4%, and 9.7% for placebo, 150 mg once daily and 200 mg twice daily, respectively.

Additional efficacy and safety endpoints for the patients enrolled in the Violet PETAL study were measured through one year of continuous dosing as well as a period of time after the final dose. The one-year dosing portion of this study concluded in May 2015 and the findings from this portion of the trial were consistent with the safety and efficacy results from the placebo-controlled portion of the Violet PETAL study.

The second Phase III study of elagolix in endometriosis is the Solstice study. This study is similar in design to the Violet PETAL study with the same co-primary endpoints of daily non-menstrual pelvic pain and daily dysmenorrhea, comparing the third month of treatment to the respective daily baseline scores utilizing a responder analysis. This trial enrolled 815 women with moderate to severe endometriosis-associated pain at more than 200 sites globally. After six months of continuous treatment, both doses of elagolix (150 mg once daily and 200 mg twice daily) met the study’s co-primary endpoints of reducing scores of non-menstrual pelvic pain and dysmenorrhea associated with endometriosis at month three, as well as at month six.

The observed safety profile of elagolix in the Solstice study was consistent with observations from prior studies. Among the most common adverse events were hot flash, headache and nausea.  While most adverse events were similar across treatment groups, some, such as hot flash and bone mineral density loss were dose-dependent. Overall discontinuation rates were similar across treatment groups and discontinuations specifically due to adverse events were 6.1%, 4.4%, and 10.0% for placebo, 150 mg once daily and 200 mg twice daily, respectively.

AbbVie is targeting a 2017 New Drug Application filing with the FDA for elagolix in endometriosis.