How common were transaminase elevations in fezolinetant trials?

Published

In the Phase 3 trials, SKYLIGHT 1, 2, and 4, elevations in hepatic transaminases (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]) > 3 × upper limit of normal (ULN) occurred in 2.3% of women receiving fezolinetant 45 mg and 0.9% of women receiving placebo

  • In the pooled laboratory data of SKYLIGHT 1, 2, and 4, elevated hepatic transaminases (> 3 × ULN) occurred in 25 women exposed to fezolinetant 45 mg (n=1100, 912.1 total person-years).1,2 This is equivalent to 2.3% of the treatment group, with an exposure adjusted incidence rate (EAIR; the number of individuals experiencing an adverse event divided by exposure time [total person-years] × 100) of 2.7. This compares with eight women (0.9%, 1.5 EAIR) exposed to placebo (n=952, 549.1 total person-years).

  • In the post-marketing setting, cases of serious drug-induced liver injury occurred within 40 days of starting fezolinetant.1 Patients experienced elevated transaminases (up to 50 × ULN at peak elevation), elevated alkaline phosphatase (up to 4 × ULN at peak elevation), and bilirubin (up to 5 x ULN at peak elevation). Patients reported a general sense of feeling unwell and symptoms of fatigue, nausea, pruritis, jaundice, pale feces, and dark urine. The patients’ signs and symptoms gradually resolved after discontinuation of fezolinetant.
    • Because these adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

  1. VEOZAH [package insert]. Northbrook, IL, USA: Astellas Pharma, Inc. Available at: https://www.astellas.com/us/system/files/veozah_uspi.pdf.

  2. Kagan R, Cano A, Nappi RE, et al. Safety of Fezolinetant for Treatment of Moderate to Severe Vasomotor Symptoms Due to Menopause: Pooled Analysis of Three Randomized Phase 3 Studies. Adv Ther. 2024. https://dx.doi.org/10.1007/s12325-024-03073-8.

find-my-msl

Find My MSL

Medical Science Liaisons are available to help answer your scientific questions.

submit

Submit an Inquiry

For any medical inquiries, please submit your question online to Astellas Medical Information or call or fax your inquiry.

Astellas Phone: 1-800-727-7003

Fax: 1-877-829-7942

adverse

Report an Adverse Event or Product Complaint

Report adverse events and product complaints to Astellas or FDA MedWatch.

Astellas Phone: 1-800-727-7003

FDA MedWatch: 1-800-FDA-1088

Hours: M–F, 8 AM–4:30 PM (CT)