AbbVie Submits New Drug Application to FDA for Elagolix in Combination with Low-Dose Hormone Therapy for Heavy Menstrual Bleeding Associated with Uterine Fibroids

Compiled by: Fan Dongdong

AbbVie and partner Neurocrine Biosciences announce submission of New Drug Application (NDA) to the U.S. FDA for Elagolix in combination with low-dose hormones for the treatment of heavy menstrual bleeding (HMB) associated with uterine fibroids in women.

Elagolix is an orally administered, non-peptide small-molecule gonadotropin-releasing hormone (GnRH) receptor antagonist that inhibits endogenous GnRH signaling by competitively binding to GnRH receptors in the pituitary gland. Administration results in dose-dependent suppression of luteinizing hormone and follicle-stimulating hormone, thereby reducing serum concentrations of ovarian sex hormones, including estradiol and progesterone. In July 2018, the drug received FDA approval for the treatment of women with moderate to severe pain associated with endometriosis. Notably, Elagolix is the first oral therapy approved by the FDA for this indication in a decade.

The new drug application for elagolix is based on data from Phase 3 clinical trials in uterine fibroids. Two pivotal studies, ELARIS UF-I and ELARIS UF-II, evaluated the efficacy of elagolix in nearly 800 premenopausal women with heavy menstrual bleeding (HMB) associated with uterine fibroids in the United States and Canada. ELARIS UF-I assessed the safety, tolerability, and efficacy of elagolix monotherapy (300 mg twice daily) over six months, while ELARIS UF-II evaluated the safety, tolerability, and efficacy of elagolix combined with low-dose hormone therapy (estradiol 1.0 mg/norethindrone acetate 0.5 mg) over six months.

The results showed that, compared with placebo, the Elagolix group exhibited a reduction in heavy menstrual bleeding (HMB) and a statistically significant decrease in total menstrual blood loss. Symptom relief was achieved by 68.5% and 76.2% of patients with uterine fibroids, respectively, after 6 months of treatment. In both studies, Elagolix combined with low-dose hormone therapy met the primary endpoint.

The most common adverse events (≥5%) reported in the two studies were hot flashes, night sweats, nausea, headache, and fatigue. The clinical study results were previously announced at the 47th AAGL Global Congress on Minimally Invasive Gynecologic Surgery of the American Association of Gynecologic Laparoscopists (AAGL), with detailed results to be published later this year in a peer-reviewed medical journal.

Results from another Phase 3 extension study (MI2-816) demonstrated that elagolix (300 mg twice daily) in combination with low-dose hormone therapy (estradiol 1.0 mg/norethindrone acetate 0.5 mg) reduced heavy menstrual bleeding in 87.9% of patients with uterine leiomyomas at Month 12. These findings were consistent with those observed in two pivotal Phase 3 clinical trials. The secondary endpoint results from the extension study were also consistent with those observed in the pivotal studies.

The safety information from the expanded trial was consistent with the previously reported top-line results from the pivotal Phase 3 clinical study, with no new safety signals identified.

To date, research on the use of Elagolix for managing heavy menstrual bleeding associated with uterine fibroids is still ongoing, and its safety and efficacy have not yet been evaluated by any regulatory authority.

Reference Source: AbbVie Submits New Drug Application to US FDA for Investigational Elagolix for Management of Heavy Menstrual Bleeding Associated with Uterine Fibroids in Women

Original Title: AbbVie Submits New Indication Application for Elagolix to Treat Heavy Menstrual Bleeding Associated with Uterine Fibroids