Elinzanetant, a new combined neurokinin-1/-3 receptor antagonist for the treatment of postmenopausal vasomotor symptoms

ABSTRACT

Introduction

In many postmenopausal women, quality of life is decreased due to vasomotor symptoms. Efficient and well-tolerated non-hormonal treatment options are needed.

Areas covered

The present review summarizes what is known about the etiology of postmenopausal vasomotor symptoms as a rationale for the mechanism of action of Elinzanetant, a new neurokinin (NK)-1/-3 receptor antagonist, as well as its efficacy and side effect profile.

Expert opinion

Elinzanetant likely exerts an antagonistic effect on the NK-3 receptor in the preoptic thermoregulatory zone, but also an additional antagonistic effect on the NK-1 receptor possibly leading to a reduction in vasodilatation and heat-sensing neuro-activity. Elinzanetant’s reported peak drug concentrations are reached within one hour and the terminal elimination half-life is approximately 15 hours. Two phase IIb clinical trials evaluated the safety profile and efficacy of several doses. There were no serious adverse events, which also included a lack of evidence of drug-related hepatotoxicity. Overall, Elinzanetant seems to be well-tolerated. In the SWITCH-1 study, the 120 mg/day and 160 mg/day regimen showed good efficacy for the treatment of vasomotor symptoms and led to significant improvements in quality of life. Thus, 120 mg oral Elinzanetant/day was used in phase III trials, whose results have not yet been published.

KEYWORDS:

• Menopause
• neurokinin
• NT-814
• sleep
• vasomotor symptoms

Article highlights

• Elinzanetant is a new neurokinin (NK)-1/-3 receptor antagonist for the treatment of menopausal vasomotor symptoms.

• Elinzanetant’s reported peak drug concentrations are reached within one hour and the terminal elimination half-life is approximately 15 hours.

• Two phase IIb clinical trials evaluated the safety profile and efficacy of several doses.

• There were no serious adverse events, which also included a lack of evidence of drug-related hepatotoxicity.

• Elinzanetant seems to be well-tolerated and efficient in reducing the severity and frequency of hot flashes.

Declaration of Interest

J Ott declares receiving fees for lecturing from Bayer, Lenus Pharma, Exeltis, and Gedeon Richter. 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 of this manuscript has disclosed being on the Advisory boards for Bayer and Astellas. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.