Pooled Safety Analysis Supports Elinzanetant for Vasomotor Symptoms Through 52 Weeks

A pooled analysis of key clinical trials of the novel dual neurokinin-1,3 (NK-1,3) receptor antagonist elinzanetant demonstrates that the 120-mg oral medication maintains a favorable safety profile through 52 weeks of treatment for vasomotor symptoms of menopause.

During the 2025 Annual Meeting of The Menopause Society (TMS), October 21-25, investigators presented pooled safety data from 690 US women with moderate-to-severe vasomotor symptoms across 4 studies that found treatment-emergent adverse events (TAEAs) occurred at comparable rates between elinzanetant (50.2%) and placebo (47.0%).¹

When adjusted for treatment exposure, AE rates were actually lower in elinzanetant-treated participants (169.67 per 100 subject-years [SY]) than in those treated with placebo (187.61 per 100 SY). Most AEs proved mild or moderate in severity, according to the study abstract.¹ The TMS meeting is being held in Orland, FL.

Elinzanetant Clinical Development Program

Elinzanetant addresses the underlying neurotransmitter pathways involved in hot flashes rather than relying on hormonal mechanisms. The compound advanced through a systematic development program that established both optimal dosing and clinical efficacy before this comprehensive safety analysis.

The optimal 120 mg dose was determined by the phase 2b SWITCH-1 study.¹ Subsequently, the phase 3 OASIS-1 and OASIS-2 studies demonstrated elinzanetant's efficacy in reducing the frequency and severity of vasomotor symptoms (VMS) and improving sleep disturbances and quality of life compared with placebo in women experiencing 50 or more VMS episodes per week.² The OASIS-3 study further supported sustained efficacy and safety over 52 weeks in women with no requirement for a minimum number of VMS events.²

Pooled Analysis

The analysis included 690 women aged 40 to 65 years, with 516 in the elinzanetant 120 mg group and 347 in the placebo group. The total exceeds 690 as the elinzanetant group includes patients who switched from placebo after 12 weeks in OASIS-1 and OASIS-2.¹

Safety Outcomes

Over 52 weeks, 259 elinzanetant-treated participants (50.2%) and 163 placebo-treated participants (47.0%) experienced TEAEs, according to the study. The exposure-adjusted incidence rates (EAIRs) for TEAEs were 169.67 per 100 subject-years in elinzanetant-treated patients and 187.61 per 100 subject-years in placebo-treated patients.¹

The most frequently reported TEAEs were COVID-19 infection (4.3% elinzanetant [EAIR: 10.01/100 SY], 5.5% placebo [EAIR: 12.70/100 SY]) and headache (4.8% elinzanetant [EAIR: 9.95/100 SY], 2.9% placebo [EAIR: 8.38/100 SY].¹

According to the study abstract, 30 participants experienced a severe TEAE (elinzanetant 18, placebo 12). Twenty-two patients reported a serious TEAE (elinzanetant 15, placebo 7). A total of 51 participants discontinued the study as a result of TEAEs.¹

Safety Signals of Interest

Researchers observed 7 cases of somnolence on elinzanetant (1.4% [EAIR: 2.76/100 SY]) compared with one case on placebo (0.3% [EAIR: 0.46/100 SY]). Five of these cases were mild, and all resolved.

Among participants treated with elinzanetant, investigators reported, hepatic enzyme elevations included a single case of abnormal alanine aminotransferase levels, increased alkaline phosphatase and increased blood bilirubin, plus 3 cases of increased aspartate aminotransferase. All hepatic enzyme elevations were mild and subsequently resolved.¹

The research team concluded that this pooled analysis of data from US women across four studies supports the safety of elinzanetant 120 mg for the treatment of moderate-to-severe vasomotor symptoms in postmenopausal women. Elinzanetant was well tolerated for up to 52 weeks of treatment, with most treatment-emergent adverse events mild or moderate in severity.¹

References

1. 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.

2. Jennings S. Bayer submits NDA for FDA for elinazentant for treatment of VMS. Patient Care. August 6, 2024. Accessed October 5, 2025. https://www.patientcareonline.com/view/bayer-submits-nda-to-fda-for-elinzanetant-for-treatment-of-vms