General Information

Orilissa (elagolix) is a gonadotropin-releasing hormone (GnRH) receptor antagonist.

Orilissa is specifically indicated for the management of moderate to severe pain associated with endometriosis.

Orilissa is supplied as a tablet for oral administration. Exclude pregnancy before starting Orilissa or start Orilissa within 7 days from the onset of menses. Take Orilissa at approximately the same time each day, with or without food. Use the lowest effective dose, taking into account the severity of symptoms and treatment objectives. Limit the duration of use because of bone loss. In patients with normal liver function or mild hepatic impairment, the recommended dose is 150 mg once daily for up to 24 months or 200 mg twice daily for up to 6 months. In patients with moderate hepatic impairment the recommended dose is 150 mg once daily for up to 6 months.

Mechanism of Action

Orilissa (elagolix) is a GnRH receptor antagonist that inhibits endogenous GnRH signaling by binding competitively to GnRH receptors in the pituitary gland. Administration of Orilissa results in dose-dependent suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to decreased blood concentrations of the ovarian sex hormones, estradiol and progesterone.

Clinical Trial Results

The FDA approval of Orilissa was based on two multinational double-blind, placebo-controlled trials in 1,686 premenopausal women [Study EM-1 and Study EM-2]. The efficacy of Orilissa 150 mg once daily and 200 mg twice daily was evaluated for the management of moderate to severe pain associated with endometriosis. The co-primary efficacy endpoints were (1) the proportion of subjects whose dysmenorrhea responded to treatment at Month 3 and (2) the proportion of subjects whose pelvic pain not related to menses (also known as non-menstrual pelvic pain) responded to treatment at Month 3. A higher proportion of women treated with Orilissa 150 mg once daily and 200 mg twice daily were responders for daily menstrual pain and non-menstrual pelvic pain compared to placebo in a dose-dependent manner at month three. Women were defined as responders if they experienced a reduction in daily menstrual pain and non-menstrual pelvic pain with no increase in analgesic use for endometriosis-associated pain. Both Orilissa treatment groups showed statistically significant greater mean decreases from baseline compared to placebo in daily menstrual pain and non-menstrual pelvic pain at month six. Patients in the studies also provided a daily self-assessment of their endometriosis pain using a numeric rating scale (NRS). The women taking Orilissa 150 mg once daily and 200 mg twice daily reported a statistically significant reduction from baseline in NRS scores compared to placebo at month three. Clinical trial data also demonstrated women taking Orilissa 200 mg twice daily showed statistically significant greater reduction in pain with sex from baseline to month three compared to placebo.