Elinzanetant: Advancing Treatment for Vasomotor Symptoms

Vasomotor symptoms (VMS) of menopause, such as hot flashes and night sweats, can cause significant discomfort for patients, and nonhormonal methods to treat these symptoms often only have modest benefit. However, a new medication, elinzanetant (Lynkuet; Bayer), was approved by the FDA on October 24, 2025, to treat VMS, and may have a greater effect in managing these symptoms.¹

What Is Elinzanetant?

Elinzanetant is a selective neurokinin-1 and neurokinin-3 receptor antagonist. Overactivity of the kisspeptin/neurokinin B/dynorphin (KNDy) neurons in the thermoregulatory location of the hypothalamus is thought to contribute to VMS. This overactivity is due to decreased estrogen levels during menopause or during antiestrogen treatment. Antagonizing the neurokinin-1 and neurokinin-3 receptors helps to regulate their activity and reduce overactivity.²

Fezolinetant (Veozah; Astellas) works similarly to elinzanetant as a neurokinin-3 antagonist and was approved by the FDA for the treatment of VMS in 2023. It is important to note that fezolinetant has a black box warning for hepatotoxicity added in December 2024. This was added because of a postmarketing report of a patient who had elevated liver laboratory test results and signs and symptoms of liver injury. This case report led to new recommendations for increased monitoring of liver blood tests: monthly testing for the first 2 months, followed by the previously recommended monitoring at 3, 6, and 9 months.³

OASIS Clinical Trials: Phase 3 Evidence for Elinzanetant

Three phase 3 trials evaluated the safety and efficacy of elinzanetant for the treatment of menopause-related hot flashes: OASIS-1 (NCT05035095), OASIS-2 (NCT05132088), and OASIS-3 (NCT05030584). OASIS-1 and OASIS-2 had very similar study designs, looking at the effect of 120 mg of elinzanetant daily or a matching placebo for 12 weeks, followed by all participants receiving 120 mg of elinzanetant for 14 weeks. OASIS-3 also had a similar design with a longer treatment duration: 52 weeks of 120 mg of elinzanetant or a matching placebo. OASIS-1 and OASIS-2 had more restrictive eligibility criteria, requiring participants to experience at least 50 moderate to severe VMS episodes during the 7-day screening period. In contrast, OASIS-3 did not require participants to meet a minimum number of VMS episodes within a given week.^4,5

OASIS-3 was a double-blind, placebo-controlled, randomized trial. Participants were included if they were naturally or surgically postmenopausal women aged 40 to 65 years seeking treatment for moderate to severe VMS. Participants were excluded if they had abnormal liver parameters; disordered proliferative endometrium; endometrial polyp, hyperplasia, or malignant neoplasm; and current cancer or a history of cancer within the past 5 years (excluding basal and squamous cell skin tumors). The primary end point of this study was the mean change from baseline to week 12 regarding the frequency of daily moderate to severe VMS.⁵

The mean number of moderate to severe VMS events per day at baseline was 6.7 (95% CI, 5.9-7.5) and 6.8 (95% CI, 6.1-7.5) for the elinzanetant and placebo arms, respectively. The mean change from baseline to week 12 for moderate to severe VMS events per day was −5.4 (95% CI, −6.3 to −4.5) for the elinzanetant group and −3.5 (95% CI, −4.1 to −2.9) for the placebo group. The least-squares mean difference in change from baseline to week 12 was statistically significant with a difference of −1.6 (95% CI, −2.0 to −1.1; P <.001). Longitudinally by week 50, participants experienced an average of 1.4 (95% CI, 1.1-1.7) and 3.5 (95% CI, 2.8-4.2) moderate to severe VMS events per day in the treatment vs placebo arms, respectively.⁵

The most commonly reported adverse events for both arms were headache, COVID-19, fatigue, somnolence, and nasopharyngitis. Of note, there was a higher rate of study discontinuation in the treatment group compared with the placebo group (12.5% vs 4.1%).⁵ There were no cases of liver enzyme elevations meeting the criteria for liver injury in the OASIS-1 and OASIS-2 trials.⁴ In OASIS-3, there were cases of liver enzyme level elevation: 6 in the treatment arm and 4 in the placebo arm. These elevations were all determined to be nonserious and were mild except for 1 event, which was considered to be moderate. Five of the cases in the treatment group resolved, and the final case had an unknown outcome. Notable limitations to the OASIS-3 study were the lack of an active drug comparator and the lack of representation of Asian or Native Pacific Islander participants.⁵

Is Elinzanetant a Safe Nonhormonal Option for Menopause?

Overall, elinzanetant serves as a viable nonhormonal therapy option for managing vasomotor symptoms of menopause with a statistically significant difference compared to placebo for reduction in the number of VMS events per day. Although elinzanetant is mechanistically similar to fezolinetant, it has the added benefit of not requiring liver monitoring as frequently, with the recommendation of only monitoring liver function tests at baseline, 3 months after initiation, and when symptoms suggest liver injury.⁶ Ultimately, more research is necessary to determine the long-term effects of this medication, as well as how elinzanetant directly compares with other medications used to treat vasomotor symptoms of menopause.

REFERENCES

1. Drug trials snapshots: Lynkuet. FDA. Updated December 30, 2025. Accessed March 3, 2026. https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-lynkuet

2. Lee A. Elinzanetant: first approval. Drugs. 2026;86(1):121-125. doi:10.1007/s40265-025-02244-3

3. FDA adds warning about rare occurrence of serious liver injury with use of Veozah (fezolinetant) for hot flashes due to menopause. FDA. Updated December 20, 2024. Accessed March 3, 2026. https://www.fda.gov/drugs/drug-safety-and-availability/fda-adds-warning-about-rare-occurrence-serious-liver-injury-use-veozah-fezolinetant-hot-flashes-due#

4. Pinkerton JV, Simon JA, Joffe H, et al. Elinzanetant for the treatment of vasomotor symptoms associated with menopause: OASIS 1 and 2 randomized clinical trials. JAMA. 2024;332(16):1343-1354. doi:10.1001/jama.2024.14618

5. 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. 2025;185(11):1319-1327. doi:10.1001/jamainternmed.2025.4421

6. Lynkuet. Prescribing information. Bayer HealthCare Pharmaceuticals Inc; 2025. Accessed March 3, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219469s000lbl.pdf