Clinical Trials

Date: 2016-02-10

Type of information: Results

phase: 3

Announcement: results

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:

• The first Phase 3 trial (M12-665) was a 24-week, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of Elagolix in 872 women, age 18 to 49, with moderate-to-severe endometriosis-associated pain. It was conducted at approximately 160 sites in the United States, Puerto Rico and Canada.
• The second Phase 3 trial (M12-671) employed the same design as the first Phase 3 pivotal trial but was multinational and included 815 women with moderate-to-severe endometriosis-associated pain across 226 sites in 13 countries (US and 12 Ex-US countries). There was equal representation of enrollment from US and Ex-US countries. Together, these two Phase 3 pivotal studies evaluated the safety and efficacy of Elagolix in nearly 1700 women with moderate-to-severe endometriosis associated pain, representing the largest prospective randomized endometriosis trials conducted to date.

Latest news:

• • On February 10, 2016,  AbbVie , in cooperation with Neurocrine Biosciences, announced results from the second of two replicate pivotal Phase 3 clinical trials evaluating the efficacy and safety of elagolix in premenopausal women who suffer pain from endometriosis (M12-671) . Trial results show that 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. Elagolix reduced scores of menstrual pain (dysmenorrhea, DYS) and non-menstrual pelvic pain (NMPP) associated with endometriosis, at month three and month six, as measured by the Daily Assessment of Endometriosis Pain scale. Responder rates for the co-primary endpoints from this second Phase 3 pivotal study are consistent with results from the first Phase 3 pivotal study.
• Table 1. Proportion of Responders for Co-Primary Endpoints

  Treatment Arm	PROPORTION OF RESPONDERS AT MONTH 3 & MONTH 6* – n (%)
  	Dysmenorrhea		Non-Menstrual Pelvic Pain
  	Month 3	Month 6	Month 3	Month 6
  Placebo (N = 353, 355) Elagolix 150 QD** (N = 221)	80 (22.7)   96 (43.4)	90 (25.4)   102 (46.2)	129 (36.5)   110 (49.8)	144 (40.6)   114 (51.6)
  Elagolix 200 BID*** (N = 225)	163 (72.4)	173 (76.9)	130 (57.8)	140 (62.2)
  p-values vs. placebo (150 QD)	<0.001	<0.001	0.003	0.010
  p-values vs. placebo (200 BID)	<0.001	<0.001	<0.001	<0.001

  *LOCF analysis also accounts for rescue analgesic use

  ** QD = once daily

  *** BID = twice daily

  The safety profile of Elagolix in this study was consistent with observations from the first Phase 3 pivotal study and prior Elagolix studies. Among the most common treatment-emergent adverse events (TEAEs) were hot flush, headache, and nausea. As anticipated by the mechanism of action, some adverse events, such as hot flush, other hypoestrogenic TEAEs and changes in bone mineral density (BMD) were dose-dependent. Overall discontinuation rates were similar across treatment groups (25.3%, 21.2%, and 19.7% for placebo, 150 mg once daily and 200 mg twice daily, respectively); discontinuations specifically due to TEAEs were 6.1%, 4.4%, and 10.0% for placebo, 150 mg once daily and 200 mg twice daily, respectively. The mean percent change from baseline in BMD at the lumbar spine (LS) at month six is provided in Table 2 below. The BMD finding for Elagolix 150 mg QD is consistent with observations from prior Phase 2 studies and as expected, a dose-dependent effect is seen for Elagolix 200 mg BID. Table 2. Mean Percent Change from Baseline in Bone Mineral Density at Lumbar Spine (Month 6)

  Mean % Change from Baseline at Lumbar Spine (Month 6)
  Placebo (n = 269)	Elagolix 150 QD (n = 174)	Elagolix 200 BID (n = 180)
  0.49 (0.20, 0.78)	-0.71 (-1.07, -0.35)	-2.45 (-2.81, -2.10)
  Between Group Comparison vs. Placebo at Month 6
  N/A	-1.20 (-1.67, -0.74)	-2.95 (-3.41, -2.49)
  	P value vs. PBO (<0.001 for both doses)

  AbbVie intends to present detailed results from its two Phase 3 trials at a future medical conference in 2016. AbbVie will complete the clinical database in anticipation of a New Drug Application submission for endometriosis in 2017.    

Is general: Yes