Elinzanetant Update: Phase 3 Findings Published in JAMA with PDUFA Date Set for October 26

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Results from the phase 3 OASIS-3 clinical trial of elinzanetant for the treatment of vasomotor symptoms of menopause were published this week in JAMA Internal Medicine, just weeks ahead of the anticipated FDA PDUFA date for the novel dual neurokinin-1 and neurokinin-3 receptor antagonist.

The original PDUFA date was July 26, 2025, but the FDA extended this deadline by up to 90 days on July 25, 2025, for a fuller review of the submitted information. Bayer announced the extension, stating that the agency did not raise concerns about the general approvability of the drug, but needed more time to complete its review. 

Bayer submitted the New Drug Application (NDA) for elinzanetant in August 2024 based on positive data from the OASIS 1, 2 and 3 phase 3 studies evaluating the efficacy and safety of the investigational compound elinzanetant versus placebo. Results from OASIS 1 and 2 were published in August 2024 in The Journal of the American Medical Association (JAMA). Detailed results of the OASIS 3 study, which provided supporting efficacy and additional long-term safety data, were first presented at the 2024 annual meeting of The Menopause Society (TMS) and are now presented in the JAMA sister publication.

"This 52-week OASIS-3 study was to our knowledge the first phase 3 clinical trial to evaluate elinzanetant for treating VMS beyond 6 months of use in postmenopausal women, with no eligibility requirement for a minimum number of moderate to severe VMS events per week," researchers wrote in the study published online September 8, 2025.1

The study included 628 postmenopausal women aged 40 to 65 years across 83 sites in North America and Europe. Participants were randomly assigned to receive either 120 mg of elinzanetant or placebo once daily. The absence of a minimum requirement for number of weekly distinguished OASIS-3 from other research and broadened the clinical relevance of the findings to a wider clinical population.1

Findings

Significant reduction in hot flashes. At week 12, women receiving elinzanetant experienced a mean reduction of 5.4 moderate to severe VMS events per day (95% CI, −6.3 to −4.5), compared to 3.5 events per day in the placebo group (95% CI, −4.1 to −2.9). The least-squares mean difference was −1.6 (95% CI, −2.0 to −1.1; P <.001), representing a 73.8% reduction in VMS frequency for elinzanetant versus 47.0% for placebo.1

Improvements in sleep and quality of life. Although the study was not powered to detect statistical significance for secondary endpoints, descriptive analyses showed numerical improvements in sleep disturbance and menopause-related quality of life1:

• Sleep Disturbance (PROMIS SD-SF-8b T score):
  • Elinzanetant: −9.4 (95% CI, −10.7 to −8.0)

• Placebo: −5.7 (95% CI, −7.0 to −4.5)

• Menopause-Specific Quality of Life (MENQOL score):
  • Elinzanetant: −1.3 (95% CI, −1.5 to −1.1)
  • Placebo: −1.1 (95% CI, −1.3 to −0.9)

“Elinzanetant, the first dual neurokinin-1 and 3 receptor antagonist to complete phase 3 testing, has shown promising results. This yearlong study not only confirmed the initial findings of rapid and significant reduction in the frequency and severity of hot flashes and night sweats but also provided evidence that these effects were sustained over a year, offering hope for longer-term relief,” lead author JoAnn V. Pinkerton, MD, director of midlife health, UVA Health, emeritus executive director, North American Menopause Society, said in a press release.2

Safety profile. Elinzanetant was generally well tolerated. Treatment-related adverse events (TEAEs) were reported in 30.4% of participants receiving elinzanetant, compared to 14.6% in the placebo group. The most common TEAEs included1:

• Somnolence (5.1%)
• Fatigue (6.7%)
• Headache (9.6%)

Serious TEAEs occurred in 4.2% of the elinzanetant group and 1.9% of the placebo group, with none considered treatment-related. No cases of endometrial hyperplasia or malignant neoplasms were reported. Bone mineral density remained stable, and no hepatotoxicity signals were detected.1

"This longer-term trial built on the findings from OASIS-1 and OASIS-2, suggesting that elinzanetant has the potential to be a well-tolerated treatment option for menopausal women with moderate to severe VMS," investigators concluded.

References:

1. Panay N, Joffe H, Maki PM, et al. Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: A Phase 3 Randomized Clinical Trial. JAMA Intern Med. Published online September 08, 2025. doi:10.1001/jamainternmed.2025.4421
2. Drug Reduces Hot Flashes by 73%, Trial Finds. News release. UVA Health. September 16, 2025. Accessed September 19, 2025. https://newsroom.uvahealth.com/2025/09/16/drug-reduces-hot-flashes-by-73-trial-finds/