Linzagolix: a new GnRH-antagonist under investigation for the treatment of endometriosis and uterine myomas

ABSTRACT

Introduction

Uterine myomas and endometriosis are benign hormone-dependent diseases affecting women of reproductive age. Substantial efforts have been made to develop innovative medical options for treating these gynecologic diseases. Elagolix and relugolix have been approved in some countries for treating endometriosis and myomas, respectively; however, linzagolix (OBE 2109, KLH 2109) is a new oral gonadotropin-releasing hormone (GnRH) antagonist in phase II–III trials. Treatment options for women with contraindications for hormonal therapies or who refuse particular options, are the driving force behind the development of new drugs in this area.

Area covered

This drug evaluation highlights definitive and preliminary results from previous and ongoing studies of linzagolix for the treatment of endometriosis and myomas.

Expert opinion

Linzagolix showed a dose-dependent and rapidly reversible action on the pituitary-gonadal axis. In a recent phase II trial (EDELWEISS), linzagolix significantly reduced pain related to endometriosis and improved quality of life at single daily doses of 75–200 mg. The preliminary results of international, double-blind phase III trials (PRIMROSE 1 and 2) reported its efficacy in treating heavy menstrual bleeding related to myomas with a good safety profile. Further studies will determine the necessity of add-back therapy during long-term use of linzagolix.

KEYWORDS:

• Endometriosis
• GnRH antagonist
• heavy menstrual bleeding
• hormonal therapy
• linzagolix
• uterine myomas
• OBE 2109
• KLH 2109
• uterine myomas

Drug Summary Box

Box 1. Drug Summary Box

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.

Reviewer disclosures

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

Article Highlights

• Women with contraindications for certain hormonal therapies or who refuse particular options, are the driving force behind the development of new drugs for uterine myomas and endometriosis.

• Linzagolix is a new oral gonadotropin-releasing hormone (GnRH) antagonist under investigation in phase II-III trials.

• Linzagolix has a long half-life of approximately 15 h, which may ensure a daily single-dose administration with a more limited intraday serum estrogen variation.

• In the phase II trial (EDELWEISS), linzagolix significantly reduced pain related to endometriosis and improved quality of life at doses of 75–200 mg once daily.

• The international, double-blind phase III trials (PRIMROSE 1 and 2) reported linzagolix efficacy in treating heavy menstrual bleeding related to uterine myomas with a good safety profile.

• The need for add-back therapy during long-term use of linzagolix must be determined.

This box summarizes key points contained in the article.

Additional information

Funding

This paper was not funded.