Four Studies Build Evidence for Elinzanetant as a Safe, Effective Nonhormonal Option for Menopausal Vasomotor Symptoms

New data presented at The Menopause Society 2025 Annual Meeting in Orlando this week provide a strong and coherent picture of the efficacy, tolerability, and broad clinical applicability of elinzanetant, a dual neurokinin-1,3 (NK-1,3) receptor antagonist in late-stage development for the treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause.

Together, findings from 4 analyses, including 3 pooled data sets from the phase 3 OASIS program, confirm elinzanetant’s consistent reduction of VMS frequency and severity, improvement of sleep-related disturbances, and favorable safety profile through 52 weeks of therapy. The studies also show that benefits extend across racially diverse and clinically distinct populations, suggesting broad therapeutic potential for this nonhormonal agent as regulatory approval nears in the United States.

Consistent Efficacy Across Diverse Populations

In a pooled analysis of the OASIS-1, -2, -3, and -4 trials, Nick Panay, MBBS, and colleagues reported that elinzanetant 120 mg significantly reduced the frequency and severity of daily hot flashes and improved sleep disturbance scores across all 4 populations studied.1 Benefits were seen not only among women with frequent VMS but also among those with lower symptom burden and among women receiving endocrine therapy for hormone receptor–positive breast cancer. The authors concluded that elinzanetant demonstrates reliable, clinically meaningful reductions in menopausal VMS and associated sleep disturbance across varied demographic and clinical subgroups.

Comparable Efficacy in African American Women

A separate pooled analysis led by Genevieve Neal-Perry, MD, PhD, examined outcomes with elinzanetant treatment among African American women enrolled in OASIS-1 and OASIS-2.2 This population historically experiences more frequent and longer-lasting hot flashes than White women. Among 133 African American participants, elinzanetant significantly reduced the frequency and severity of moderate-to-severe VMS at weeks 4 and 12 compared with placebo, mirroring efficacy seen in non-African American participants. Safety profiles were similarly favorable, with treatment-emergent adverse events (TEAEs) mild or moderate in most cases. The investigators noted that these findings address an important gap in evidence for populations disproportionately affected by menopausal symptoms.

Sleep Improvements Extend Beyond Hot Flash Relief

In another pooled analysis of 4 clinical trials including more than 1,300 postmenopausal women, Pauline Maki, PhD, and colleagues used causal mediation modeling to examine whether elinzanetant’s improvements in sleep disturbances were entirely dependent on hot flash reduction.3 The team found that more than half (54.3%) of the sleep benefit occurred independently of reductions in nighttime VMS frequency, suggesting that elinzanetant exerts direct effects on sleep regulation beyond thermoregulatory symptom control. The authors emphasized that these findings challenge long-standing assumptions that menopausal sleep disturbances arise solely from VMS-related awakenings.

Safety Maintained Through One Year of Treatment

Long-term safety data from 690 US participants across 4 studies further support elinzanetant’s favorable tolerability profile.4 Reported during the meeting by James Simon, MD, and colleagues, the pooled analysis found comparable rates of TEAEs between elinzanetant (50.2%) and placebo (47.0%) over 52 weeks, with most events recorded as mild or moderate. Exposure-adjusted incidence rates of AEs were actually lower among elinzanetant-treated participants than placebo (169.67 vs 187.61 per 100 subject-years). No new safety signals emerged; mild, transient somnolence and hepatic enzyme elevations were infrequent and resolved without sequelae.

A Promising Addition to the Nonhormonal Treatment Landscape

Menopausal vasomotor symptoms affect up to 80% of women, and current nonhormonal options remain limited. By targeting both NK-1 and NK-3 receptors, elinzanetant addresses central and peripheral mechanisms implicated in thermoregulation and sleep, representing a mechanistically distinct approach from existing therapies such as the NK-3–specific antagonist fezolinetant.

Across multiple clinical analyses, elinzanetant has shown consistent efficacy, sustained safety, and potential benefits that extend beyond VMS relief. These data, taken together, establish a compelling clinical foundation for elinzanetant as a next-generation nonhormonal therapy for menopause-related vasomotor and sleep disturbances.

References

1. Panay N, Cardoso F, Simon JA, et al. Efficacy of elinzanetant 120 mg across different populations of women from four phase 3 OASIS studies. Abstract presented at: 2025 Annual Meeting of The Menopause Society; October 21-25, 2025; Orlando, FL.

2. Neal-Perry G, Dunsmoor-Su R, Trigg A, Lee A, Hendy AA, Maki P. Efficacy of elinzanetant for the treatment of vasomotor symptoms associated with menopause in US African American women: pooled data from two Phase 3 studies. Abstract presented at: The Menopause Society’s 2025 Annual Meeting; October 21-25, 2025; Orlando, FL. Accessed October 21, 2025.

3. Maki P, Trigg A, Joffe H, et al. Elinzanetant improves sleep disturbances in menopausal women partially independently of reductions in vasomotor symptoms. Abstract presented at: The Menopause Society’s 2025 Annual Meeting; October 21-25, 2025; Orlando, FL. Accessed October 21, 2025.

4. Simon JA, Kaunitz A, Francuski M, et al. Pooled safety of elinzanetant for the treatment of vasomotor symptoms associated with menopause across the US population from 4 placebo-controlled studies. Abstract presented at: 2025 Annual Meeting of The Menopause Society; October 21-25, 2025; Orlando, FL.