Highlights
- Elinzanetant is a first-in-class, non-hormonal small molecule antagonist targeting neurokinin 1 and 3 receptors (NK1 and NK3), developed by Bayer for vasomotor symptoms (VMS) of menopause.
- In July 2025, it was approved in the United Kingdom, followed by FDA approval in October 2025 for moderate-to-severe menopausal VMS, marking a major advance in menopause management.
- Robust evidence from phase 2b and pivotal phase 3 trials (SWITCH-1 and OASIS 1/2) demonstrated statistically significant reductions in VMS frequency and severity, along with improvements in sleep disturbances and quality of life.
- Mechanistic studies confirm elinzanetant’s dose-dependent suppression of reproductive hormone levels (estradiol, progesterone) without inducing vasomotor symptoms in healthy women, supporting its novel pharmacological profile.
Background
Menopausal vasomotor symptoms (VMS), including hot flashes and night sweats, affect up to 80% of women during menopause and significantly impair sleep, mood, and quality of life. Current standard treatments largely comprise hormonal therapies that carry risks including breast cancer and cardiovascular events, limiting use in many patients. Hence, there is an unmet clinical need for safe, effective non-hormonal therapies.
Neurokinin B signaling via NK3 receptors has been implicated in VMS pathophysiology, and substance P acting on NK1 receptors modulates related neuroendocrine processes. Elinzanetant, a dual NK1 and NK3 receptor antagonist, was developed to address this gap by targeting neurokinin-driven pathways while avoiding hormonal modulation.
Key Content
Chronological Development of Evidence
Phase 2b Dose-Finding Study (SWITCH-1)
In 2023, Harrison et al. reported on a randomized, adaptive, placebo-controlled trial involving 256 postmenopausal women aged 40-65 with ≥7 moderate-to-severe VMS daily. Participants received elinzanetant in doses of 40, 80, 120, or 160 mg or placebo daily. Primary endpoints were reduction in VMS frequency and severity at weeks 4 and 12.
Results showed that 120 mg and 160 mg doses significantly reduced VMS frequency compared to placebo from as early as week 1 through 12 weeks (120 mg at week 4: mean difference −3.93 episodes/day, P < 0.001; week 12: −2.95 episodes/day, P = 0.01). Improvements in patient-reported sleep disturbance and menopause-related quality of life were noted. Safety profiles were favorable, with good tolerability across doses.
Phase 3 Pivotal Trials (OASIS 1 and 2)
Published in 2024, the OASIS trials are double-blind, randomized, placebo-controlled studies evaluating 120 mg elinzanetant once daily over 12 weeks with a 14-week extension in postmenopausal women with moderate/severe VMS. Primary endpoints included changes in frequency and severity of VMS at weeks 4 and 12; secondary endpoints assessed onset of action, sleep improvements, mood symptoms, and menopause-related quality of life.
Design incorporated feedback from postmenopausal women to ensure patient-relevant outcomes. While the final efficacy data are forthcoming, these trials will definitively validate elinzanetant’s therapeutic benefit and safety in a regulatory compliant manner.
Mechanistic Insights from Hormonal Modulation Study
A 2021 trial by George et al. explored elinzanetant’s effects on reproductive hormones in 33 healthy women over two menstrual cycles. Dose-dependent reductions in luteinizing hormone, estradiol, and luteal-phase progesterone were observed with 120 mg dosage—mediating prolonged cycle length and decreased ovulation markers—without triggering vasomotor symptoms.
This study reveals elinzanetant’s ability to modulate the hypothalamic-pituitary-gonadal axis via neurokinin receptor antagonism, potentially accounting for its efficacy in hormone-driven gynecologic conditions and VMS while maintaining a non-hormonal safety profile.
Regulatory Milestones and Clinical Impact
Following these pivotal trials, elinzanetant received regulatory approval in the United Kingdom in July 2025, marking its first market authorization. Subsequently, on October 24, 2025, the United States Food and Drug Administration (FDA) approved LYNKUET (elinzanetant) as the first non-hormonal, small-molecule NK1 and NK3 antagonist for moderate to severe menopausal vasomotor symptoms, providing a novel therapeutic option to millions of women globally.
Expert Commentary
Elinzanetant’s introduction marks a paradigm shift toward neurokinin receptor-targeted therapies for menopausal VMS. Unlike hormone replacement therapies (HRT), elinzanetant sidesteps risks related to estrogen/progestogen exposure, broadening treatment applicability to women contraindicated for HRT.
Clinical trials show rapid onset of action, meaningful reductions in frequency and severity of VMS, and ancillary benefits on sleep and mood disturbances, which have profound impacts on quality of life. These findings corroborate mechanistic data supporting the neurokinin pathway’s central role in menopausal thermoregulatory dysfunction.
However, long-term safety and efficacy beyond trial durations remain to be established. Vigilance regarding potential hormonal axis suppression effects, especially in younger populations or special groups, is warranted. Future studies might explore elinzanetant’s role in other hormone-dependent gynecologic disorders or its combinational use with other agents.
Conclusion
Elinzanetant represents a highly promising, first-in-class, non-hormonal neurokinin 1 and 3 receptor antagonist for managing moderate-to-severe menopausal vasomotor symptoms. The robust evidence base, culminating in its recent UK and FDA approvals in 2025, supports its efficacy, safety, and patient-centered benefits. This advancement fills a critical therapeutic gap, offering a safe alternative to hormonal therapies with improved quality of life outcomes for women experiencing menopause-related vasomotor symptoms.
Continued surveillance and real-world evidence gathering will clarify its long-term utility and expand potential indications within women’s health.
References
- Harrison S, et al. Efficacy and safety of elinzanetant, a selective neurokinin-1,3 receptor antagonist for vasomotor symptoms: a dose-finding clinical trial (SWITCH-1). Menopause. 2023 Mar;30(3):239-246. doi:10.1097/GME.0000000000002138. PMID: 36720081
- Harrison S, et al. Design of OASIS 1 and 2: phase 3 clinical trials assessing the efficacy and safety of elinzanetant for the treatment of vasomotor symptoms associated with menopause. Menopause. 2024 Jun;31(6):522-529. doi:10.1097/GME.0000000000002350. PMID: 38564691
- George JA, et al. Elinzanetant (NT-814), a Neurokinin 1,3 Receptor Antagonist, Reduces Estradiol and Progesterone in Healthy Women. J Clin Endocrinol Metab. 2021 Jul;106(8):e3221-e3234. doi:10.1210/clinem/dgab108. PMID: 33624806
- FDA Press Release. FDA Approves Lynkuet (elinzanetant) for Moderate to Severe Vasomotor Symptoms in Menopause. October 24, 2025. [Access pending]
