Strategies and Endpoints of Antifibrotic Drug Trials #MMPMID25626988
Torok N; Dranoff JA; Schuppan D; Friedman SL
Hepatology 2015[Aug]; 62 (2): 627-34 PMID25626988show ga
There is an urgent need to develop antifibrotic therapies for chronic liver disease, and to clarify which endpoints in antifibrotic trials will be acceptable to regulatory agencies. AASLD sponsored an endpoints conference to help accelerate the efficient testing of antifibrotic agents and to develop recommendations on clinical trial design for liver fibrosis. In this review we summarize the salient and novel elements of this conference and provide directions for future clinical trial design. The paper follows the structure of the conference and is organized into five areas: I) Antifibrotic trial design; II) Preclinical proof of concept studies; III) Pharmacologic targets: rationale and lessons to learn; IV) Rational drug design and development; V) Consensus and recommendations on design of clinical trials in liver fibrosis. Expert overviews and collaborative discussions helped to summarize the key unmet needs and directions for the future, including: 1) Greater clarification of at-risk populations and study groups; 2) Standardization of all elements of drug discovery and testing; 3) Standardization of clinical trial approaches; 4) Accelerated development of improved non-invasive markers; 5) Need for exploration of potential off-target toxicities of future antifibrotic drugs.
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Hepatology 2015 ; 62 (2): 627-34
