FDA Grants Priority Review to Elinzanetant for Endocrine Therapy–Associated Vasomotor Symptoms in HR+ Breast Cancer

The FDA has granted priority review to a supplemental new drug application (sNDA) seeking approval of elinzanetant (Lynkuet) for the treatment of moderate to severe vasomotor symptoms in patients receiving endocrine therapy for the management or prevention of hormone receptor (HR)–positive breast cancer.¹

The sNDA submission was based on results from the phase 3 OASIS-4 trial (NCT05587296), in which elinzanetant met its primary end point of a statistically significant reduction in the frequency of moderate to severe vasomotor symptoms vs placebo.^1,2

“Endocrine therapy is a standard of care for many women [with] HR-positive breast cancer and can commonly cause [adverse] effects such as vasomotor symptoms,” Fatima Cardoso, MD, primary investigator of the OASIS-4 trial and director of the Breast Unit at the Champalimaud Clinical Center in Lisbon, Portugal, stated in a news release.¹

Elinzanetant is a dual neurokinin-1 (NK-1) and NK-3 receptor antagonist. Previously, it was approved by the FDA in October 2025 at a dose of 60 mg for the management of moderate to severe hot flashes during menopause, based on data from the phase 3 OASIS-1 (NCT05042362), OASIS-2 (NCT05099159), and OASIS-3 (NCT05030584) trials.

How was the OASIS-4 trial designed?

OASIS-4 was a multicenter, randomized, double-blind, placebo-controlled trial evaluating elinzanetant for the management of vasomotor symptoms associated with endocrine therapy in women with HR-positive breast cancer or at high risk of developing HR-positive breast cancer.² The trial enrolled 474 women aged 18 to 70 years who were experiencing vasomotor symptoms due to endocrine therapy (tamoxifen or an aromatase inhibitor, with or without a gonadotropin-releasing hormone analog), which they were expected to continue for the study duration. Eligible patients had a personal history of HR-positive breast cancer or were at high risk of developing breast cancer and were required to report at least 35 moderate to severe hot flashes per week at baseline.

Patients were randomly assigned 2:1 to receive elinzanetant at 120 mg (n = 316) or placebo (n = 158) during a 12-week double-blind period, after which patients in the placebo arm switched to elinzanetant through week 52; an optional 2-year extension with elinzanetant treatment followed. The primary end point was the mean change from baseline in the frequency of moderate to severe vasomotor symptoms; secondary end points included safety and changes in vasomotor symptom severity. At baseline, 55.4% of patients in the elinzanetant arm were receiving tamoxifen, and 44.6% of patients in this arm were receiving an aromatase inhibitor.

What efficacy data were observed in OASIS-4?

At baseline, the mean daily frequency of moderate to severe vasomotor symptoms was 11.4 events (95% CI, 10.7-12.2) in the elinzanetant arm and 11.5 events (95% CI, 10.5-12.5) in the placebo arm. At week 4, treatment with elinzanetant led to a mean reduction of 6.51 daily vasomotor symptom events vs 3.04 vasomotor symptom events with placebo (least squares [LS] mean difference, –3.5; 95% CI, −4.4 to −2.6; P < .0001). At week 12, the mean reduction was 7.76 events with elinzanetant vs 4.20 events with placebo (LS mean difference, −3.4; 95% CI, −4.2 to −2.5; P < .0001).

A treatment effect favoring elinzanetant was observed as early as week 1 and sustained through week 12; patients who switched from placebo to elinzanetant after the double-blind period experienced similar reductions that were maintained throughout the study. Elinzanetant also numerically reduced moderate to severe vasomotor symptom severity vs placebo, with a mean change from baseline of −0.73 vs −0.43 at week 4 and −0.98 vs −0.53 at week 12.

What was the safety profile of elinzanetant in patients with breast cancer?

During the 12-week placebo-controlled period, treatment-emergent adverse events (TEAEs) occurred in 69.8% of patients treated with elinzanetant (n = 315) vs 62.0% of those given placebo (n = 158). The most common TEAEs in the elinzanetant arm were headache (9.5%), somnolence (10.8%), fatigue (9.5%), nausea (6.0%), and arthralgia (6.3%). Serious TEAEs occurred in 2.5% of patients in the elinzanetant arm vs 0.6% of those in the placebo arm.

Over the full 52-week period, any-grade TEAEs occurred in 79.1% of elinzanetant-treated patients (N = 465), and serious TEAEs occurred in 7.1% of patients who received elinzanetant.

The investigators concluded that elinzanetant was well tolerated, with a favorable safety profile over 52 weeks, supporting its potential long-term use in this population. Additional safety data are being collected in an ongoing 2-year study extension.

References

1. US FDA accepts sNDA and grants priority review to Bayer’s Lynkuet (elinzanetant) for a new indication for the treatment of moderate to severe vasomotor symptoms due to endocrine therapy related to breast cancer. News release. Bayer. September 28, 2026. Accessed September 28, 2026. https://www.bayer.com/en-us/united-states/news-and-stories/2026/fda-accepts-snda
2. Cardoso F, Brennan DJ, Briggs P, et al. Efficacy and safety of elinzanetant for vasomotor symptoms associated with endocrine therapy: phase 3 OASIS-4 trial. J Clin Oncol. 2025;43(suppl 16):508. doi:10.1200/JCO.2025.43.16_suppl.508