TURALIO® Risk Evaluation and Mitigation Strategy (tREMS) program: 5-year retrospective hepatic safety assessment

Area of Science:

• Hepatology
• Oncology
• Pharmacovigilance

Background:

• Tenosynovial giant cell tumor (TGCT) is a rare neoplastic proliferation.
• Pexidartinib is an approved therapy for symptomatic TGCT, but carries a risk of liver injury.
• The TURALIO® Risk Evaluation and Mitigation Strategy (tREMS) program was implemented to monitor pexidartinib safety.

Purpose of the Study:

• To evaluate the hepatic safety profile of pexidartinib in adult TGCT patients.
• To assess the effectiveness of the tREMS program in managing pexidartinib-associated hepatotoxicity over five years.

Main Methods:

• Retrospective analysis of data from the tREMS program (August 2019 - June 2024).
• Inclusion of data from healthcare professionals, patients, pharmacies, and distributors.
• Assessment of adverse events and laboratory abnormalities indicative of liver injury.

Main Results:

• Over five years, 6.1% of patients (45/735) experienced liver injury; 4.6% (24/524) in the current reporting period (June 2022-June 2024).
• One patient (0.2%) in the current period developed confirmed vanishing bile duct syndrome (VBDS) and was recovering.
• The observed pattern of liver injury aligns with findings from the phase 3 ENLIVEN trial.

Conclusions:

• The tREMS program effectively mitigates pexidartinib-induced hepatotoxicity through monitoring and early intervention.
• Pexidartinib remains a valuable treatment for TGCT when administered under recommended safety guidelines.
• Continued vigilance and adherence to risk management strategies are essential for safe pexidartinib use.