The potential role of elagolix for treating uterine bleeding associated to uterine myomas

ABSTRACT

Introduction

Uterine myomas represents a widespread gynecological disease of women in reproductive age. Although surgery remains the first choice for treating most patients, in the last years, new medical approaches have been considered in order to ameliorate heavy menstrual bleeding (HMB) related to their presence. Elagolix is a second-generation gonadotropin-releasing hormone (GnRH) antagonist under investigation for the long-term treatment of uterine myomas.

Areas covered

The aim of this drug evaluation is to give a complete overview of pharmacokinetic and pharmacodynamic data on elagolix for treating HMB related to uterine myomas and to report the results of the current clinical trials in this setting.

Expert opinion

In two previous phase II studies, this drug succeeded in ameliorating blood loss and quality of life of patients affected by uterine myomas with a good safety profile. Three phase III trials (ELARIS UF-I, UF-II, and EXTEND) investigated the efficacy, tolerability, and safety of elagolix at 300 mg twice daily with add-back therapy. The primary endpoint, consisting in the reduction in HMB compared to placebo, was met in the majority of patients under treatment. Currently, elagolix is under investigation in two other ongoing multicenter phase III clinical studies.

KEYWORDS:

• Uterine leiomyomas
• uterine fibroids
• GNRH antagonist
• hormonal therapy
• elagolix
• elagolix sodium
• abnormal uterine bleeding
• heavy menstrual bleeding

Article highlights

• Uterine myomas represents a widespread gynecological disease of women in reproductive age. In the last years, new medical hormonal options, such as gonadotropin-releasing hormone (GnRH) agonists (GnRH-as) and ulipristal acetate (UPA), have been largely employed to ameliorate heavy menstrual bleeding (HMB) related to uterine myxomas.

• Elagolix is a second-generation oral GnRH antagonist recently approved for the treatment of pain related to endometriosis. Currently, this drug is under late-clinical investigation for the long-term treatment of uterine myomas.

• Irreversibly binding to pituitary receptor for endogenous GnRH, elagolix causes a rapidly and dose-dependently decreases the levels of gonadotropins and estradiol, which limit growth of uterine myomas.

• In two previous phase II studies, this drug succeeded in ameliorating blood loss and quality of life of patients affected by uterine myomas, showing a good safety profile.

• Three phase III trials (ELARIS UF-I, UF-II, and EXTEND) confirmed the efficacy, and safety of elagolix administered at 300 mg twice daily in combination with add-back therapy.

• Ongoing phase III trials will confirm the efficacy and safety of elagolix on large populations of patients with uterine myomas, definitively clarifying the need of add-back therapy under treatment.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This manuscript was not funded.