ContraVir Pharmaceuticals’ Cyclophilin Inhibitor, CRV431, Reduces Liver Fibrosis in a Preclinical Model
In the treatment of HBV infections, an important objective is the reduction of liver disease including fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Previously, studies of CRV431 have demonstrated its antiviral effects via the reduction of HBV DNA, surface antigen, and other viral markers. In the recently completed preclinical study of CRV431, mice were administered streptozotocin, followed by a high fat diet that began at three weeks of age and continued for the duration of the study. CRV431, given orally for eight weeks, had no effect on body weight, liver weight or blood glucose levels. The livers were examined throughout this experiment and revealed that CRV431 decreased the extent of fibrosis by 46 percent compared to vehicle control (p=0.03).
“The significant reduction in fibrosis development seen in this study, confirms our previous findings from a separate study conducted in Japan. Given this corroborating evidence, we see an opportunity to pursue a clinical program for CRV431 in fibrosis, expanding the potential of CRV431 beyond hepatitis B,” said
CRV431 is a non-immunosuppressive analog of cyclosporine A (CsA) whose primary biochemical action is inhibition of cyclophilin isomerases which play key roles in protein folding. Other viruses such as HIV-1 and HCV, similarly use cyclophilins for their replication. CRV431 shows potential in experimental models to complement current hepatitis B treatments by reducing multiple markers of infection including HBV DNA, HBsAg, HBeAg, and HBV uptake by cells. Studies have also demonstrated that CRV431 possesses anti-fibrotic activity which may further curb progression of liver disease in patients.
ContraVir is a biopharmaceutical company focused on the development and commercialization of targeted antiviral therapies with a specific focus on developing a potentially curative therapy for hepatitis B virus (HBV). The company is developing two novel anti-HBV compounds with complementary mechanisms of action. TXL™, designed to deliver high intrahepatic concentrations of TFV while minimizing off-target effects caused by high levels of circulating TFV (bone and kidney), recently completed a Phase 2a trial. CRV431, the other anti-HBV compound, is a next-generation cyclophilin inhibitor with a unique structure that increases its potency and selective index against HBV. In vitro and invivo studies have thus far demonstrated that CRV431 reduces HBV DNA and other viral proteins, including surface antigen (HBsAg). For more information visit www.contravir.com.
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Source: ContraVir Pharmaceuticals Inc.