Elinzanetant Shows Consistent Efficacy, Safety, and Sleep Benefits Across Studies

Elinzanetant (Lynkuet; Bayer) just became the most recent nonhormonal treatment approved for moderate to severe vasomotor symptoms (VMS) associated with menopause.1 At The Menopause Society 2025 Annual Meeting, findings from multiple Bayer-sponsored trials of elinzanetant, a dual neurokinin-1 and neurokinin-3 receptor antagonist, highlighted consistent efficacy across patient populations and strong safety for 1-year use.

In an interview with The American Journal of Managed Care® (AJMC®), James Simon, MD, CCD, MSCP, clinical professor of obstetrics and gynecology at the George Washington University School of Medicine and medical director of IntimMedicine Specialists, said the pooled US safety data provide important reassurance for clinicians.2

“It showed very clearly that elinzanetant was safe in this subset of women from the US for as long as a year,” he told AJMC. “That’s the important take-home message. Very few side effects.”

Sustained Safety in US Women

A pooled analysis of 690 US women aged 40 to 65 years included data from the phase 2b SWITCH-1 study and the phase 3 OASIS-1, OASIS-2, and OASIS-3 trials.3 Over 52 weeks, treatment-emergent adverse events (TEAEs) were observed in 50.2% of elinzanetant-treated participants compared with 47.0% of those receiving placebo, with most events mild or moderate.

Exposure-adjusted incidence rates were 169.67 per 100 subject-years with elinzanetant and 187.61 per 100 subject-years with placebo. The most common TEAEs were headache (4.8%), which Simon said is a common symptom, and COVID-19 infection (4.3%), which he said had nothing to do with the drug. No unexpected or serious safety signals emerged.

“If that’s the second most common side effect, it really speaks to how clean this therapy is in terms of side effect profile,” he said.4

He added that elinzanetant’s hepatic safety profile distinguishes it from other nonhormonal options. “The safety profile…shows no signal for an adverse effect on hepatic function—on liver—which has been a subject of great controversy in this particular space because of the adverse effects seen in a very small group of patients given fezolinetant and the FDA’s warning labels and changes to the FDA-approved labeling for fezolinetant as a reaction to those liver effects,” Simon told AJMC.2 “None of those liver effects were seen in this safety population overall or this subset of safety in American or US women.”

Now that the drug is approved, Simon noted that longer-term follow-up in separate phase 4 studies may further confirm these results.

Elinzanetant is now approved for moderate to severe vasomotor symptoms with menopause. | Image credit: DimaBerlin – stock.adobe.com

Improvements in Sleep Beyond Hot Flash Reduction

Pauline Maki, PhD, professor of psychiatry, psychology, and obstetrics and gynecology, and director of women’s mental health research at the University of Illinois Chicago, presented separate data showing elinzanetant’s ability to improve sleep disturbances in postmenopausal women.5 These improvements were partially independent of what could be explained by reductions in nighttime hot flashes, according to researchers.

Across 4 trials—OASIS-1, OASIS-2, OASIS-3, and NIRVANA—with 1345 total participants, the therapy reduced PROMIS Sleep Disturbance Short Form 8b T-scores by 4.92 points compared with placebo. Mediation analyses showed that 54.3% of the improvement in sleep was direct and independent of VMS relief, suggesting the drug acts on additional neuroendocrine pathways linked to sleep regulation.

“These findings highlight the potential for [elinzanetant] to improve sleep through mechanisms beyond VMS alleviation and support the notion that sleep disturbances in menopause are not solely caused by VMS,” Maki said. “Further research is warranted to elucidate the pathways through which [elinzanetant] exerts its direct effects on sleep.”

Consistent Efficacy Across Populations

A third pooled analysis was presented by Nick Panay, BSc, MBBS, FRCOG, MFSRH, director of the Menopause & PMS Centre at Queen Charlotte’s & Chelsea Hospital West London Gynaecological Cancer Centre in London, UK.6 The analysis showed consistent efficacy across nearly 1900 women enrolled in the OASIS-1 through OASIS-4 studies. Participants included women with naturally or surgically induced menopause and those receiving endocrine therapy for hormone receptor–positive breast cancer.

Elinzanetant 120 mg consistently reduced daily VMS frequency and severity and improved sleep quality from baseline to week 12, with greater mean changes compared with placebo across all studies. These effects were observed even among participants with lower baseline symptom burdens and in women with therapy-induced hot flashes.

“These results suggest consistent efficacy across differing populations of women, including those with a lower baseline symptom burden (OASIS-3) and those with VMS caused by endocrine therapy for the treatment of breast cancer (OASIS-4),” Panay said.

References

1. McNulty R. FDA approves elinzanetant, a hormone-free option for hot flashes in menopause. AJMC. October 24, 2025. Accessed October 24, 2025. https://www.ajmc.com/view/fda-approves-elinzanetant-a-hormone-free-option-for-hot-flashes-in-menopause
2. Klein HE, Simon J. Elinzanetant shows strong 52-week safety for vasomotor symptoms: James Simon, MD. AJMC. October 24, 2025. Accessed October 24, 2025. https://www.ajmc.com/view/elinzanetant-shows-strong-52-week-safety-for-vasomotor-symptoms-james-simon-md
3. Simon JA, Kaunitz A, Francuski M, Trigg A, Lee A, Bachmann G. Pooled safety of elinzanetant for the treatment of vasomotor symptoms associated with menopause across the US population from 4 placebo-controlled studies. Presented at: The Menopause Society 2025 Annual Meeting; October 24, 2025; Orlando, FL.
4. Simon JA. Elinzanetant demonstrates favorable safety profile in menopausal women, with James A. Simon, MD. Contemporary OB/GYN. October 24, 2025. Accessed October 24, 2025. https://www.contemporaryobgyn.net/view/elinzanetant-demonstrates-favorable-safety-profile-in-menopausal-women-with-james-a-simon-md
5. Maki P, Trigg A, Joffe H, et al. Elinzanetant improves sleep disturbances in menopausal women partially independently of reductions in vasomotor symptoms. Presented at: The Menopause Society 2025 Annual Meeting; October 24, 2025; Orlando, FL.
6. Panay N, Cardoso F, Simon JA, et al. Efficacy of elinzanetant 120 mg across different populations of women from four phase 3 OASIS studies. Presented at: The Menopause Society 2025 Annual Meeting; October 24, 2025; Orlando, FL.