Elagolix in the treatment of heavy menstrual bleeding associated with uterine fibroids in premenopausal women

ABSTRACT

Introduction

Uterine fibroids (UFs) are the most common benign tumor arising from myometrium of reproductive age women, with significant financial burden estimated in hundreds of billions of dollars. Unfortunately, there are limitations in available long-term treatment options. Thus, there is a large unmet need in the UF space for noninvasive therapeutics.

Areas covered

Authors reviewed the literature available for elagolix; an orally bioavailable, second-generation, non-peptide gonadotropin-releasing hormone (GnRH) antagonist recently approved by the US Food and Drug Administration (FDA) in combination with estradiol/norethindrone acetate for the management of heavy menstrual bleeding associated with UFs in premenopausal women.

Expert opinion

The utility of new-generation oral GnRH-antagonists, such as elagolix, relugolix and linzagolix, is offering a new potential opportunity for the future therapy of UFs: elagolix has been the most studied drug of this class for treating benign gynecological diseases, including endometriosis and UFs, for which it has been US FDA-approved in 2018 and 2020, respectively.

KEYWORDS:

• Add-back Therapy
• elagolix
• GnRH Antagonists
• heavy Menstrual Bleeding
• leiomyoma
• uterine Fibroids

Article highlights

• Uterine Fibroid has a profound impact on patients’ quality of life and health care costs worldwide.

• The mechanism underlying uterine fibroids pathogenesis remains unclear, which in turn limits its effective treatment. Current investigated treatment options aim to halt their hormonal dependent growth including gonadotropin releasing hormone (GnRH) analogs (agonists and antagonists).

• If possible, many women with UFs would choose pharmacological treatment over a surgical treatment to secure their future family plans and avoid major surgeries.

• Elagolix is an orally bioavailable, second-generation, non-peptide GnRH antagonist recently approved by the US Food and Drug Administration (FDA) in combination with estradiol/norethindrone acetate for the management of heavy menstrual bleeding associated with uterine fibroids in premenopausal women up to 24 months.

• Following elagolix discontinuation, hormonal level was found to return rapidly to normal values along with restoration of menstruation, which represents an advantage for women pursuing future fertility.

Declaration of interest

A. Al-Hendy has declared consultancy for Allergan, Bayer, Repros and Myovant Sciences, as well as AbbVie. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed having served on advisory boards for Bayer AG and Gedeon Richter. AbbVie provided a scientific accuracy review at the request of the journal editor. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This study was supported in part by the National Institutes of Health grants: R01 HD094378-04, R01 ES 028615-02, R01 HD100367-01, U54 MD007602, and R01 HD094380-02