Fezolinetant: a novel nonhormonal therapy for vasomotor symptoms due to menopause

ABSTRACT

Introduction

During menopause, the majority of women experience vasomotor symptoms which may lead to several untoward effects and negatively impact quality of life. Fezolinetant, a novel agent directly targeting the underlying pathophysiology of menopause-associated vasomotor symptoms, offers an alternative to hormonal therapies for which many patients have a contraindication or unwillingness to take due to safety concerns.

Areas covered

This review summarizes key pharmacologic, pharmacokinetic, and pharmacodynamic parameters of fezolinetant along with efficacy and safety data derived from clinical trials. A literature search of peer-reviewed publications evaluating the efficacy and safety of fezolinetant was conducted using PubMed and EMBASE databases. A review of registered trials in clinicaltrials.gov was evaluated to identify ongoing studies.

Expert opinion

Placebo-controlled studies demonstrated that fezolinetant led to a statistically significant reduction in vasomotor symptom frequency and severity among patients with moderate-to-severe vasomotor symptoms. The most common adverse event is headache (5–10%) and no serious safety signals have been noted. Direct head-to-head comparison with hormonal therapies and nonhormonal therapies for vasomotor symptoms, assessment of sleep outcomes, and evaluation of efficacy and safety beyond 1 year are key areas where additional data are still needed.

KEYWORDS:

• Fezolinetant
• hot flashes
• menopause
• neurokinin 3 receptor antagonist
• nonhormone therapy
• vasomotor symptoms

Article highlights

• Effective nonhormone therapy options to alleviate sustained, bothersome vasomotor symptoms (VMS) due to menopause are essential, particularly for women who are unable or unwilling to receive hormone therapy.

• Fezolinetant available as a once daily oral tablet is a novel, nonhormonal neurokinin 3 receptor antagonist that directly targets the pathophysiologic process contributing to VMS.

• Clinical efficacy evaluated in placebo-controlled studies demonstrated that fezolinetant led to a statistically significant reduction in vasomotor symptom frequency and severity among patients with moderate-to-severe vasomotor symptoms.

• Given study findings, fezolinetant appears to be safe and well-tolerated, with headache identified as the most frequent adverse event.

• Direct head-to-head comparison with hormonal therapies and nonhormonal therapies for VMS, assessment of sleep outcomes, and evaluation of efficacy and safety beyond 1 year are key areas where additional data are still needed.

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

A reviewer on this manuscript has disclosed being the Chief Investigator in the following trials: Skylight 1 and Oasis 4. Another reviewer has disclosed being the Lead Principal Investigator for Bayer’s Elinzanetant. They have also undergone medical education on fezolinetant and vasomotor symptoms. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.