When did transaminase elevations occur in fezolinetant trials?

Published

Prescribing Information including BOXED WARNING

In the Phase 3 SKYLIGHT 1, 2 and 4 clinical trials of fezolinetant, there was no apparent cluster of time to onset of transaminase elevation across treatment groups, and there was no clear pattern of rise and fall of transaminase values

Onset of elevations in liver chemistry for alanine aminotransferase (ALT), aspartate aminotransferase (AST), or bilirubin occurred at various timepoints throughout the study duration.¹
In the post-marketing setting, cases of serious drug-induced liver injury occurred within 40 days of starting fezolinetant.² 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.

Across SKYLIGHT 1, 2 and 4, the incidence of ALT and/or AST > 3 x upper limit of normal (ULN) was 0.9% in the placebo group and 2.3% in the fezolinetant 45 mg group.³ There were no Hy’s law cases (defined as ALT or AST > 3 × ULN with concomitant total bilirubin > 2 × ULN with no elevation of ALP, and no other reason to explain the combination), an indicator of drug-induced liver injury.
Women with ALT or AST elevations were generally asymptomatic. Transaminase levels returned to pretreatment levels (or close to these) without sequelae with dose continuation, and upon dose interruption, or discontinuation.¹

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