Mouse Model Continues to Show Efficacy of GKT831 for Treating Cholestatic Fibrosis in Primary Biliary Cholangitis

Preclinical data supporting the efficacy of GKT831 as a potential therapy for cholestatic fibrosis has just been published in the Journal of Hepatology.


GKT831 is both a NOX1 enzyme and NOX4 enzyme inhibitor. It is one of the product candidates being developed by Genkyotex, targeting various NOX enzymes. GKT831 is not new news. It’s efficacy has already been established in previous mouse models for both fibrotic and inflammatory diseases. The selective inhibition of the NOX enzymes has been shown to decrease fibrosis. This is because NOX enzymes in the body amplify many disease processes including inflammation, cancer, pain processing, neurodegeneration, and fibrosis.

Severe cholestatic fibrosis is unfortunately common in primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC). This recent preclinical data utilizing a MDR2 KO mouse model is so important because the model accurately portrayed advanced stage cholestatic fibrosis, which these patients often face. Fortunately, the data from this mouse model continued to show the efficacy of GKT831. In the model, the researchers waited until the advanced fibrosis was established before the treatment was administered (week 12). After only four weeks, fibrosis was reversed in the mice and the myofibroblasts were deactivated. In other words, anti-fibrotic activity was clearly and rapidly achieved. These findings aligned with the data gathered from an ongoing clinical trial for PBC.

Phase 2 Clinical Trial

In the active Phase 2 clinical trial evaluating GKT831 for primary biliary cholangitis patients, after a mere 24 weeks of treatment, liver stiffness was reduced. For those who had severe fibrosis, there was a 21% reduction. Additionally, those patients given a 400mg BID dose, achieved a 2.7 kPa absolute reduction. Those in the placebo group had a .4 kPa increase. The results from this recent mouse model for advanced cholestatic fibrosis which was just completed continue to support these findings.

Ongoing Research

Currently, GKT831 is also in a Phase 2 clinical trial evaluating its efficacy for Type 1 Diabetes and Kidney Disease. Additionally, Victor Thannickal, a professor at the University of Alabama at Birmingham (UAB) is working to further evaluate the role of NOX enzymes in idiopathic pulmonary fibrosis (IPF). This research is being funded by a 8.9 million dollar grant awarded by the NIH.

Ultimately, this additional preclinical data utilizing a mouse model supports not only the potential, but the continued development and investigation of GKT831 in PBC, PSC, IPF, and other fibrotic conditions.

You can read more about GKT831 and NOX inhibitor research here.

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