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 the 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 due to 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 18 to 70 years of age 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 changes in vasomotor symptom severity, and safety. 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 VM 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 was sustained through week 12; patients who switched from placebo to elinzanetant after the double-blind period experienced similar reductions, which were maintained throughout the duration of 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 AEs (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 the course of 52 weeks that supports 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 25, 2026. Accessed September 26, 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