AbbVie Files New Drug Application for its GnRH Antagonist

By Rajaneesh K. Gopinath, Ph.D.

Elagolix, an investigational, oral gonadotropin-releasing hormone (GnRH) antagonist had previously received USFDA approval for endometriosis-associated pain management. Promising data obtained with the drug with add-back therapy from a phase III study involving 800 patients have resulted in the global biopharma pursue USFDA approval for another indication.

On August 5^th, AbbVie together with the cooperation of Neurocrine Biosciences, Inc., announced their submission of a new drug application for Elagolix (ORILISSA™) for the management of heavy menstrual bleeding (HMB) in women associated with uterine fibroids. Uterine fibroids are non-cancerous growths in the uterus that often appear in women during their childbearing years. These tumors are mostly asymptomatic and do not usually lead to uterine cancers. However, they are hormonally responsive and, in some women, symptoms such as HMB, extended menstrual period and frequent urination appears. Current treatment options for this condition include surgery, endometrial ablation, uterine artery embolization, magnetic resonance imaging (MRI)-guided ultrasound etc.

Mode of Action

Elagolix is an orally-administered, non-peptidic, small molecule drug that competitively binds to GnRH receptors in the pituitary gland and thereby inhibits endogenous GnRH signaling. The drug suppresses the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in a dose-dependent manner and inturn decreases the levels of estradiol and progesterone. Last year, Elagolix was USFDA approved for use in the management of moderate to severe pain associated with endometriosis in premenopausal women. It is also currently tested for the treatment of various diseases caused by ovarian sex hormones.

ELARIS UF-I and ELARIS UF-II Studies

The submission is a result of promising data from the Elagolix Phase III uterine fibroid program. It comprised of two pivotal studies, ELARIS UF-I (n=412) and ELARIS UF-II (n=378), which evaluated nearly 800 premenopausal women with HMB associated with uterine fibroids. The studies evaluated the safety, tolerability and efficacy of Elagolix alone, and in combination with a low-dose hormone (add-back) therapy. The primary endpoint assessed the reduction in HMB compared to placebo and both studies showed that Elagolix with add back therapy met that.

As expected for a drug that alters hormonal levels, the most common side effects included hot flush, night sweats, nausea, headache and fatigue. The results from these studies were announced at the 47th American Association of Gynecologic Laparoscopists (AAGL) Global Congress on Minimally Invasive Gynecology held at Las Vegas, Nevada.

Michael Severino, M.D., vice chairman and president of AbbVie, shared his views on the NDA. “This submission brings us closer to our goal of improving care for women who continue to struggle with the often disruptive effects of uterine fibroids,” he said. “If approved, this combination has the potential to offer women and their healthcare providers an additional oral medical treatment option.”

References

1. https://news.abbvie.com/news/press-releases/abbvie-submits-new-drug-application-to-us-fda-for-investigational-elagolix-for-management-heavy-menstrual-bleeding-associated-with-uterine-fibroids-in-women.htm
2. https://news.abbvie.com/news/abbvie-receives-us-fda-approval-orilissa-elagolix-for-management-moderate-to-severe-pain-associated-with-endometriosis.htm

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Author

Rajaneesh K. Gopinath