Clinical Trials

Date: 2017-11-01

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the American Society for Reproductive Medicine Scientific Congress & Expo (ASRM)

Company: Abbvie (USA - IL) Neurocrine Biosciences (USA - CA)

Product: elagolix

Action mechanism:

• GnRH receptor antagonist. Elagolix is an orally administered gonadotropin-releasing hormone (GnRH) antagonist that is currently being investigated in diseases that are mediated by sex hormones, such as uterine fibroids and endometriosis.

Disease: endometriosis

Therapeutic area: Women health

Country:

Trial details:

• Elaris EM­III and Elaris EM­IV are two extension studies of the six month pivotal, Phase 3 studies (Elaris EM-I and Elaris EM-II) that evaluated an additional six months of treatment, for an overall treatment period of 12 months, with two elagolix doses (150 mg once daily and 200 mg twice daily). Study participants were women, age 18-49, with surgically diagnosed endometriosis and moderate to severe endometriosis-associated pain at baseline during the pivotal trials. Baseline values for these analyses were assessed prior to dosing in the pivotal studies.

Latest news:

• • On November 1, 2017, AbbVie in cooperation with Neurocrine Biosciences announced detailed results from two replicate Phase 3 extension studies evaluating the long-term efficacy and safety of elagolix, an investigational, orally administered gonadotropin-releasing hormone (GnRH) antagonist, being evaluated for the management of endometriosis with associated pain.
• In the extension studies, elagolix demonstrated sustained reduction in average monthly menstrual pelvic pain and non-menstrual pelvic pain in women through the 12-month treatment period. The safety and tolerability of elagolix was consistent with the anticipated effects of reduced estradiol levels and no new safety concerns were identified with elagolix use for the 12-month treatment period1. These results, and other additional abstracts, were presented at the American Society for Reproductive Medicine Scientific Congress & Expo (ASRM) in San Antonio.
• The objective of the extension studies was to evaluate the long-term safety and efficacy of elagolix for the management of endometriosis with associated pain. The efficacy endpoints of the pivotal studies were the proportion of responders based on the average monthly menstrual pain (dysmenorrhea) and non-menstrual pelvic pain scores, as measured by the Daily Assessment of Endometriosis Pain scale. The reductions in dysmenorrhea and non-menstrual pelvic pain following six months of elagolix treatment were maintained over six additional months of treatment (12 months total) across both extension studies for both 150 mg once daily (QD) and 200 mg twice daily (BID) doses.1 More than 50 percent of women were responders for dysmenorrhea and non-menstrual pelvic pain at both doses.1 The responder rate for painful intercourse (dyspareunia) after 12 months was higher with the 200 mg BID dose than with 150 mg QD dose2, which reflects a dose-dependent effect similar to the effect reported in pivotal studies.
• Safety assessments in the extension studies included evaluation of adverse events, along with clinical laboratory tests and changes in bone mineral density.1,6 The safety profile of elagolix was consistent with the partial hormone suppression associated with its mechanism of action. The proportion of women with new incidences of hot flush ranged between 4-8 percent across both studies and doses.1 A dose-dependent average decrease from baseline in bone mineral density (0.6% and 1.1% with 150 mg QD in EM-III and EM-IV, respectively; and 3.6% and 3.9% with 200 mg BID in EM-III and EM-IV, respectively) was observed at month 12.6 After 12 months of treatment, one woman on the 200 mg BID dose had a BMD z-score below -2.0,which is the age-adjusted normal threshold.15 All of the women on the 150 mg QD dose had a BMD z-score within the age-adjusted normal threshold.15 Findings were consistent across both Phase 3 extension trials and no new safety concerns were identified with long-term elagolix use.
• AbbVie conducted multiple oral presentations at ASRM highlighting the results of the Phase 3 extension studies1,2,6,7, as well as research on the direct healthcare utilization and costs associated with endometriosis among women with Medicaid insurance in the United States.8 AbbVie also presented efficacy and safety data from a Phase 2b clinical trial evaluating elagolix alone or in combination with add-back therapy (estradiol/norethindrone acetate) compared to placebo in women with uterine fibroids.

Is general: Yes