GENFIT SA (GNFT) has announced its strategic plans to initiate two new clinical trials in the first quarter of 2025, focusing on its Acute-on-Chronic Liver Failure (ACLF) pipeline. The company anticipates multiple data readouts by the end of the year, marking 2025 as a pivotal year for advancements in addressing unmet medical needs in liver disease.
The new trials are designed based on insights gained throughout 2024, including AI-driven analysis of real-world evidence and input from key opinion leaders (KOLs). These insights aim to streamline trial execution and enhance patient recruitment, particularly focusing on patients with acute decompensation (AD) at high risk of progressing to ACLF.
Clinical Trial Details
The first trial will evaluate VS-01 in patients with AD or ACLF grade 1 who have overt Hepatic Encephalopathy (HE) grades 2, 3, or 4, and ascites. This proof-of-concept study will enroll 21 patients with a treatment duration of up to 4 days. The primary endpoint is the time to improvement in overt HE, with secondary endpoints including safety, tolerability, and pharmacokinetic/pharmacodynamic parameters. Exploratory endpoints will assess blood ammonia levels, inflammatory markers, and other clinical outcomes.
The second trial will assess NTZ, using G1090N, a new formulation developed in 2024, in patients with AD at risk of progressing to ACLF or ACLF grade 1. This study will also enroll 21 patients with a treatment duration of 7 days. The primary endpoint is safety and tolerability, with secondary endpoints focusing on pharmacokinetic and pharmacodynamic parameters. Exploratory endpoints will include inflammatory and clinical markers.
A third study, a First-in-Human trial with a new formulation of SRT-015, is set to launch following final analyses of preclinical data expected in 1Q25. Pending positive analysis, pharmacokinetic and pharmacodynamic assessments will be conducted in healthy volunteers, with clinical data readout anticipated by late 2025.
Data Readouts Anticipated
GENFIT anticipates four clinical data readouts by the end of 2025. These include the UNVEIL-IT Phase 2 trial, which evaluates VS-01, and data from the Phase 1b trial evaluating GNS561 in combination with trametinib in patients with KRAS-mutated cholangiocarcinoma. The Phase 1b data will support dose selection for a Phase 2 trial.
Strategic Insights and Collaborations
The trial designs are informed by advanced real-world evidence analysis, including AI-driven evaluation of medical claims data from over 270,000 U.S. patients. This analysis has uncovered ACLF risk profiles, referral dynamics, and management practices. Key perspectives from the ACLF KOL Advisory Board and ongoing engagement with the European Foundation for the Study of Chronic Liver Failure (EF CLIF) have also contributed to the strategic development of the ACLF pipeline.
Dr. Jonel Trebicka, MD, PHD, Head of Department and Professor of Medicine, University of Münster, Germany, noted, "It makes sense for GENFIT to evaluate its assets in a subset of patients with AD having specific comorbidities that contribute to a particularly poor prognosis... AD and ACLF are very dynamic syndromes sharing key pathophysiological mechanisms."
Dr. Jacqueline O’Leary, Chief of Hepatology at the Dallas VA Medical Center and Professor of Medicine at UTSW, USA, added, "ACLF should be viewed as a continuum. Real-world evidence showed that some patients with acute decompensation face a high risk of mortality. Therefore, it is crucial to include this specific patient group when evaluating drug candidates."
