FDA Green-Lights Elinzanetant, First Dual NK-1/NK-3 Antagonist, for Moderate to Severe Vasomotor Symptoms of Menopause

The US FDA has approved the investigational agent elinzanetant, the first dual neurokinin-1 (NK-1) and neurokinin-3 (NK-3) receptor antagonist, for the treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause.1

The approval marks a long-awaited nonhormonal oral treatment alternative for women whose hot flashes or night sweats are significant and who are unable or unwilling to use hormone therapy.1

“For more than a century, Bayer has been dedicated to pioneering advances in women’s health, and this FDA approval represents a bold step forward – our first hormone-free treatment for alleviating vasomotor symptoms of menopause,” Christine Roth, executive vice president, global product strategy and commercialization and member of the pharmaceutical leadership team at Bayer, said in a statement. “There is a need for more individualized approaches to menopause care, and [elinzanetant] addresses a significant gap in treatment options.”1

Millions Enter Menopause Every Year

The global population of women experiencing menopause is projected to increase to 1.2 billion by 2030, which translates to 47 million women entering this phase of life each year.2

VMS affect up to 60%-80% of women during the menopausal transition, with roughly one-third reporting severe symptoms that persist for years.3 Many women either delay seeking treatment or receive therapies with limited efficacy or tolerability. Many women prefer to pass on traditional hormone replacement therapy (HRT) and for others, the treatment is contraindicated. Current nonhormonal options offer suboptimal relief.4,5

Phase 3 OASIS Development Program

The FDA's approval is based on a phase 3 clinical program (OASIS 1, 2 and 3) which enrolled post-menopausal women aged 40-65 years experiencing moderate to severe VMS. In OASIS 1/2, women received once-daily oral elinzanetant 120 mg or placebo for 26 weeks; key endpoints included mean change in frequency and severity of VMS at weeks 4 and 12. OASIS 3, a 52-week double-blind randomized study (n = 628), confirmed sustained reductions in VMS frequency along with improvements in sleep disturbances and menopause-related quality of life. A recent meta-analysis found that elinzanetant significantly reduced the frequency of VMS compared with placebo (mean difference –23.1 episodes; 95 % CI –24.2 to –22.0) and improved intensity and sleep disturbance scores.1

“These three studies investigated the safety and efficacy of elinzanetant for the treatment of moderate to severe hot flashes due to menopause,” JoAnn Pinkerton, MD, Professor and Director of Midlife Health at UVA Health and Lead Investigator on the OASIS 2 trial, said. “Hot flashes, particularly when severe, can have an impact on women’s daily lives and this approval provides healthcare providers with a new treatment option that can be used first-line for moderate to severe hot flashes due to menopause.”1

Pinkerton spoke with Patient Care© to discuss the full read out of results from the OASIS 1 and 2 trials.

Elinzanetant works by targeting the hypothalamic “thermostat” pathway. With declining estrogen levels, the so-called KNDy neurons (kisspeptin/neurokinin B/dynorphin) in the hypothalamus become hypertrophic and trigger inappropriate activation of thermoregulatory systems via NK-3 and NK-1 receptor signaling. By antagonizing both NK-3 and NK-1, elinzanetant aims to reduce the frequency and severity of VMS by dampening that hyperactivation and modulating associated vasodilatation and heat-sensing neuroactivity.1

In contrast, as Pinkerton noted in a separate interview with Patient Care, hormone therapy acts peripherally by replenishing estrogen vs elinzanetant's central recalibration.

In terms of safety, the overall elinzanetant profile was favorable across the clinical trial program, with most adverse events being mild to moderate (for example headache, fatigue) and no safety signals that halted development. A recent pooled safety analysis of elinzanetant clinical trials found treatment emergent adverse events comparable between the NK-1/NK-3 antagonist and placebo through 52 weeks of treatment.1

“It’s important that women know they have choices for treating moderate to severe hot flashes due to menopause, and today’s approval further expands a woman’s options for treating these symptoms,” Claire Gill, President and Founder of the National Menopause Foundation, added in the Bayer statement.

Bayer AG submitted the New Drug Application for elinzanetant in October 2024, based on the positive OASIS studies. The company said it expects elinzanetant to be available in the US as early as November.1

References

1. Bayer’s Lynkuet (elinzanetant) approved in the U.S. for treatment of moderate to severe vasomotor symptoms due to menopause. News release. Bayer. October 24, 2025. Accessed October 24, 2025. https://www.bayer.com/media/en-us/bayers-lynkuet-elinzanetant-approved-in-the-us-for-treatment-of-moderate-to-severe-vasomotor-symptoms-due-to-menopause/

2. Global leaders launch declaration on menopause calling World Health Organization and national governments to develop first-ever policies and guidance to support menopausal women. News release. Power Menopause. October 20, 2025. Accessed October 24, 2025.

3. Avis NE, Crawford SL, Green R. Vasomotor symptoms across the menopause transition: differences among women. Obstet Gynecol Clin North Am. 2018;45(4):629-640. doi:10.1016/j.ogc.2018.07.005

4. Thurston RC, Joffe H. Vasomotor symptoms and menopause: findings from the Study of Women's Health across the Nation. Obstet Gynecol Clin North Am. 2011;38(3): 489–501. doi: 10.1016/j.ogc.2011.05.006

5. Thurston RC. Vasomotor symptoms: natural history, physiology, and links with cardiovascular health. Climacteric. 201821(2):96-100. doi:10.1080/13697137.2018.1430131