FDA approves elinzanetant for menopausal hot flushes, with liver reporting attached

The Food and Drug Administration approved Lynkuet (elinzanetant) capsules on 24 October for the treatment of moderate to severe vasomotor symptoms due to menopause [s1][s4]. Bayer HealthCare Pharmaceuticals had filed the application on 26 July 2024, and a major amendment dated 22 July 2025 extended the review goal date by three months [s1].

The trials behind the approval were built around a stated gap: an unmet need for long-term, safe, effective and hormone-free treatments for menopausal symptoms, including vasomotor symptoms and sleep disturbance [s2][s3].

What elinzanetant is

Elinzanetant is a selective neurokinin-1,3 receptor antagonist — it blocks two receptors rather than one [s3]. The first neurokinin-targeting drug for menopausal vasomotor symptoms to reach the US market, fezolinetant, was approved as Veozah under priority review on 12 May 2023 [s4].

The approved elinzanetant product is a 60 mg oral capsule [s4].

The evidence

Three phase 3 trials underpin the application.

OASIS 1 and OASIS 2 were randomised, double-blind trials in postmenopausal participants aged 40 to 65 with moderate to severe vasomotor symptoms, conducted at 77 sites each — OASIS 1 in the US, Europe and Israel, and OASIS 2 in the US, Canada and Europe [s3]. Participants received once-daily oral elinzanetant 120 mg for 26 weeks, or placebo for 12 weeks followed by elinzanetant 120 mg for 14 weeks [s3].

In OASIS 1, 199 participants were randomised to elinzanetant and 197 to placebo; in OASIS 2, 200 and 200 [s3]. Elinzanetant significantly reduced the frequency of vasomotor symptoms at week 4 (OASIS 1: −3.3; 95% CI, −4.5 to −2.1; OASIS 2: −3.0; 95% CI, −4.4 to −1.7; both P<.001) and at week 12 (OASIS 1: −3.2; 95% CI, −4.8 to −1.6; OASIS 2: −3.2; 95% CI, −4.6 to −1.9; both P<.001) [s3]. Symptom severity also improved at week 12, by −0.4 (95% CI, −0.5 to −0.3) in OASIS 1 and −0.3 (95% CI, −0.4 to −0.1) in OASIS 2, against baseline severity scores of 2.6 and 2.5 in the elinzanetant groups [s3]. Sleep disturbance and menopause-related quality of life improved at week 12, and the safety profile was described as favourable [s3].

OASIS-3 ran longer and enrolled more broadly. It was a 52-week, double-blind, placebo-controlled trial at 83 sites in North America and Europe, running from 27 August 2021 to 12 February 2024, in postmenopausal women aged 40 to 65 seeking treatment for moderate to severe vasomotor symptoms — with no requirement for a minimum number of events per week [s2]. That last detail matters: it admits women with less frequent symptoms than efficacy trials usually enrol.

A total of 313 women were randomised to elinzanetant and 315 to placebo, with mean ages of 54.6 and 54.9 [s2]. At week 12, the mean change from baseline in daily moderate to severe vasomotor symptom frequency was −5.4 (95% CI, −6.3 to −4.5) with elinzanetant and −3.5 (95% CI, −4.1 to −2.9) with placebo, a least-squares mean difference of −1.6 (95% CI, −2.0 to −1.1; P<.001) [s2].

The placebo arm is worth pausing on. Placebo alone cut symptom frequency by 3.5 per day; the drug added 1.6 on top of that [s2]. Both numbers are real, and quoting only the −5.4 would misrepresent what the drug contributes.

The safety picture, and what FDA did about it

OASIS-3 reported that elinzanetant was not associated with hepatotoxic effects, endometrial hyperplasia, or meaningful changes in bone density or bone turnover markers [s2]. Treatment-related adverse events were more common with elinzanetant than placebo, at 30.4% versus 14.6%, most frequently somnolence, fatigue and headache [s2].

The trial's own framing is restrained. Its authors note that no statistical hypotheses were defined for the secondary and exploratory endpoints, and that the study was not powered to detect between-group differences on them — so the sleep and quality-of-life findings over 52 weeks were descriptive [s2]. Their conclusion is that elinzanetant "shows promise" [s2].

Against that, the approval letter asks for something specific. FDA requested enhanced pharmacovigilance: all serious and non-serious, domestic and foreign cases of hepatic adverse events including liver injury are to be submitted as 15-day alert reports through the third year following initial US approval [s1]. The agency set explicit reporting thresholds, including ALT or AST greater than eight times the upper limit of normal; ALT or AST greater than three times the upper limit with total bilirubin greater than twice the upper limit; ALT or AST greater than three times the upper limit with symptoms suggestive of hepatic disease; any hepatic adverse event leading to discontinuation; and any hepatic event term denoting a diagnosis, jaundice, liver injury, or non-infectious hepatitis [s1].

Bayer must also provide a narrative analysis of hepatic adverse events, including a medical literature review, in its periodic safety reports through the third year after approval [s1].

The gap between no hepatotoxic effects observed in OASIS-3 and three years of intensified liver-injury surveillance is not a contradiction. It is what a regulator does when a trial population is too small to exclude an uncommon harm in a drug intended for widespread, elective, long-term use.

Process notes

The application was not referred to an advisory committee; FDA stated that outside expertise was not necessary and there were no controversial issues that would benefit from such discussion [s1]. The pediatric study requirement was waived because the necessary studies would be impossible or highly impracticable [s1]. The expiry dating period is 30 months from manufacture at 20°C to 25°C [s1].

What to watch

The hepatic reports FDA has asked for, and whether the class's real-world safety record over three years matches its trial record [s1]. And whether the sleep benefits suggested descriptively in OASIS-3 are confirmed in a trial designed to test them [s2].

This article describes a regulatory action and the trials behind it. It is not treatment advice, and decisions about menopausal symptom treatment belong with a clinician.

Sources

• [s1] NDA 219469 Approval Letter — Lynkuet (elinzanetant) capsules, U.S. Food and Drug Administration, 24 October 2025. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2025/219469Orig1s000ltr.pdf
• [s2] Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: A Phase 3 Randomized Clinical Trial (OASIS-3), JAMA Internal Medicine, 8 September 2025. https://doi.org/10.1001/jamainternmed.2025.4421
• [s3] Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: OASIS 1 and 2 Randomized Clinical Trials, JAMA, 22 August 2024. https://doi.org/10.1001/jama.2024.14618
• [s4] Drugs@FDA: NDA 219469 (Lynkuet) and NDA 216578 (Veozah) — approval records, U.S. Food and Drug Administration. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=219469