Every sheriff needs a deputy: targeting non-parenchymal cells to treat hepatic fibrosis

The landscape of anti-fibrotic drug development for liver disease is littered with failed clinical trials. In 2020, the CCR2 and CCR5 receptor antagonist, Cenicriviroc, failed to achieve its primary endpoint of fibrosis improvement of ≥1 stage without worsening of steatohepatitis at 12 months despite promising preclinical and phase 2 data[1]. This failure was particularly disappointing as it was one of the most promising immune-targeted therapeutics to reach phase 3 testing. In 2023, the FXR agonist, obeticholic acid, met the p rimary endpoint that Cenicriviroc could not, but the FDA voted against its approval for treatment of pre-cirrhotic liver fibrosis due to metabolic dysfunction-associated steatohepatitis (MASH) citing a lack of evidence of long-term efficacy[2].
Source: Journal of Hepatology - Category: Gastroenterology Authors: Tags: Editorial Source Type: research