Elagolix for Endometriosis Pain Receives FDA Approval

The US Food and Drug Administration (FDA) has granted approval to AbbVie and Neurocrine Biosciences, Inc.’s elagolix (Orilissa), the first oral gonadotropin-releasing hormone (GnRH) antagonist developed for women with moderate to severe endometriosis pain.

"Orilissa represents a significant advancement for women with endometriosis and physicians who need more options for the medical management of this disease," Michael Severino, MD, Executive Vice President, Research and Development and Chief Scientific Officer, AbbVie said in a statement. "The approval of Orilissa demonstrates AbbVie's continued commitment to address serious diseases and unmet needs."

The FDA approval of elagolix was supported by data from 2 large phase 3 studies that included close to 1700 premenopausal women with the moderate to severe endometriosis.

The 6-month studies, Elaris Endometriosis I and II [EM-I and EM-II], tested 2 doses of elagolix, 150 mg once daily and 200 mg twice daily, compared to placebo. The primary efficacy end points were the proportion of participants who had a clinical response with respect to dysmenorrhea and the proportion who had a clinical response with respect to nonmenstrual pelvic pain at 3 months.

"Endometriosis is often characterized by chronic pelvic pain that can impact women's daily activities," said Hugh S. Taylor, MD, study investigator and Chair of the Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine. "Women with endometriosis may undergo multiple medical treatments and surgical procedures seeking pain relief and this approval gives physicians another option for treatment based on a woman's specific type and severity of endometriosis pain."

In Elaris EM-1, 46.4% of women in the low-dose group and 75.8% in the high-dose group had a clinical response with respect to dysmenorrhea, compared to 19.6% in the placebo group. For the second study, the respective percentages were 43.4% and 72.4%, compared with 22.7% (p <0.001 for all comparisons).

For the primary efficacy endpoint relating to nonmenstrual pelvic pain, women in Elaris EM-1 responded at rates of 50.4% (low-dose) and 54.5% (high-dose) compared to 36.5% (placebo). In Elaris EM-2, those rates were 49.8% and 57.8% compared to 36.5% in placebo.

In the Elaris EM-1 and EM-2 studies, more than 70% of participants reported at least 1 adverse event. However, 10% or less of the women left the study due to any adverse event. The 3 most frequently reported adverse events were hot flushes, headache, and nausea.

In November 2017, AbbVie announced results from 2 extension studies, Elaris EM-3 and Elaris EM-4 that evaluated the long-term efficacy and safety of elagolix for the treatment of pain related to endometriosis.

Participants in the 6-month extension studies continued receiving either the low-dose, high-dose, or placebo. Over 50% of women responded to treatment for dysmenorrhea and nonmenstrual pelvic pain at both dose levels.

Elagolix is recommended for use up to 24 months at the 150 mg once daily dose and up to 6 months at the 200 mg twice daily dose. Greater duration is not recommended due to a dose-dependent decrease in bone mineral density.

The label warns that the possible serious side effects of elagolix are suicidal thoughts, actions, or behaviors, and abnormal liver tests. The most common side effects listed include hot flashes, night sweats, headache, nausea, difficulty sleeping, absence of periods, anxiety, joint pain, depression, and mood changes.

"Together with AbbVie, we are proud to offer a treatment option for the many women suffering from pain associated with endometriosis," said Kevin Gorman, PhD, Chief Executive Officer of Neurocrine Biosciences. "Neurocrine discovered Orilissa nearly 20 years ago and through our partnership with AbbVie, the approval of Orilissa reflects our joint commitment to develop therapies for difficult to manage conditions in underserved patient populations."

In September 2017, AbbVie submitted a New Drug Application to the FDA for elagolix. The next month, the FDA granted elagolix Priority Review status. The company expects elagolix to be available in retail pharmacies across the US in early August 2018.