(C-246) Safety and Utilization of Fezolinetant for Menopause Symptoms

Background: Veozah (fezolinetant) is a novel, non-hormonal neurokinin 3 (NK3) receptor antagonist approved by the FDA in May 2023 for the treatment of moderate-to-severe vasomotor symptoms from menopause. Little is known about the real-world utilization and treatment-related adverse events of fezolinetant, especially in older women and women with a breast cancer history.

Objectives: The objectives of this study were to characterize fezolinetant utilization and examine the rate of hepatic adverse events with fezolinetant use.

Methods: This retrospective cohort study was conducted using the TriNetX data in January 2025. We included female patients ≥18 years old with a prescription for fezolinetant (RxNorm code 2637134) between June 1, 2023, and November 1, 2024. Sub-cohorts included women ≥65 years old at the time of fezolinetant initiation and women with an ICD-10-CM code for breast cancer or history of breast cancer. The main outcome was hepatic adverse events in the year after fezolinetant initiation. Hepatic adverse events were defined using ICD-10-CM codes for toxic liver disease and abnormal serum enzyme levels. We conducted descriptive statistics and determined the proportion of patients with treatment-related outcomes.

Results: The total number of fezolinetant prescriptions increased rapidly over time, from 489 prescriptions in the June-August 2023 quarter to 2,812 prescriptions in the September-November 2024 quarter. Our cohort included 7,283 women with a fezolinetant prescription, among whom 1,202 (16.5%) had three or more prescriptions during their follow-up time (i.e., persistent users), 1,118 (15.4%) were ≥65 years old and 1,363 (18.7%) had a breast cancer diagnosis. Most patients had a prior prescription for hormone replacement therapy (36% with a vaginal estrogen prescription, 35.8% with an estrogen prescription, and 26.4% with a progestin prescription). In the overall cohort, 1.9% of patients had a code for a hepatic adverse event. In the sub-cohorts, 2.4% of those ≥65 years old and 2.3% of those with a breast cancer diagnosis had a code for a hepatic adverse event in the year after fezolinetant initiation. We found that 9.8% of fezolinetant initiators and 10.6% of persistent users in our cohort had a code indicative of metabolic dysfunction-associated steatotic liver disease (vs. 0.6% of patients in the pooled cohort from the fezolinetant trials). Among persistent users, only 68% received liver function testing in the year after initiating fezolinetant, though regular hepatic laboratory testing (i.e., at baseline and months 1, 2, 3, 6, and 9 after starting treatment) is required after starting treatment.

Conclusions: We found evidence of hepatic adverse events in the year after fezolinetant initiation, with a greater proportion of hepatic adverse events among older women and those with a breast cancer diagnosis. More research is needed to examine access to liver function testing and adherence to the recommended intervals for testing. It is also important that future studies examine the safety and utilization among women with baseline liver disease.