AbbVie, a global, research-based biopharmaceutical company, in cooperation with Neurocrine Biosciences, Inc., announced positive top-line 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.
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.
"Endometriosis affects an estimated 176 million women worldwide. Patients voice their frustration about the need for more treatment options to medically manage endometriosis and its often debilitating pain," said Michael Severino, M.D. executive vice president, research and development, and chief scientific officer, AbbVie.
"In an effort to address this need, AbbVie conducted the largest clinical trials in endometriosis to date. We are pleased with the outcomes of the pivotal trials thus far. AbbVie will continue to pursue Elagolix as a potential new treatment for the disease's most common symptoms, including pain related to menstruation and chronic pelvic pain throughout the menstrual cycle."
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 AEs, 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 per cent, 21.2 per cent, and 19.7 per cent for placebo, 150 mg once daily and 200 mg twice daily, respectively); discontinuations specifically due to TEAEs were 6.1 per cent, 4.4 per cent, and 10.0 per cent for placebo, 150 mg once daily and 200 mg twice daily, respectively. The mean per cent changed from baseline in BMD at the lumbar spine (LS) at month six. 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.
The top-line results are from a six-month, group-level analysis. Patients in the trial will continue on in either post-treatment follow-up or a blinded extension study for an additional six-month safety and efficacy evaluation. 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.
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, aged 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.
This 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.
Endometriosis occurs when the cells that normally line the uterus begin to grow outside of the uterus. These growths are called lesions and can occur on the ovaries, the fallopian tubes, or other areas near the uterus. There is no cure for endometriosis, which is currently managed with oral contraceptives, NSAIDs, opioids, and GnRH agonists. When these medical treatments fail, surgical interventions (e.g., laparotomy or laparoscopy) are often pursued, and again, are not curative. Endometriosis can also be associated with infertility.
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. To date, Elagolix has been studied in over 40 clinical trials totaling more than 3,000 subjects. Phase 3 trials of Elagolix for the management of uterine fibroids are also ongoing.