Genkyotex (Euronext Paris & Brussels: FR0013399474 – GKTX), a biopharmaceutical company and the leader in NOX therapies, today announced the presentation of additional data from the Phase 2 trial of setanaxib in primary biliary cholangitis (PBC).

These latest results show that in patients with elevated liver stiffness (≥9.6 kPa corresponding to the histological fibrosis stage ≥ F3), setanaxib reduced type III collagen formation and induced type III collagen degradation, resulting in a net reduction of collagen accumulation. Collagen III is the main collagen type secreted by activated myofibroblasts.

As a reminder, the key finding of the PBC Phase 2 trial (see press releases from June 24 and July 25, 2019) was the rapid reduction in liver stiffness (-20.9% for setanaxib vs +4% for placebo, p<0.05) in patients with elevated liver stiffness (≥ 9.6 kPa), i.e. those with advanced liver fibrosis.

Fibrosis progression is primarily caused by increased collagen III formation (measured by PRO-C3, the propeptide of type III collagen) and insufficient collagen III degradation (measured by C3M). The latest results show that in the Phase 2 PBC trial, patients with elevated liver stiffness at baseline had increased PRO-C3 levels and PRO-C3/C3M ratios. After 24 weeks of treatment, setanaxib reduced PRO-C3 (collagen III formation), increased C3M (collagen III degradation) levels, and reduced the PRO-C3/C3M ratio indicating reduced collagen III net accumulation. Setanaxib also increased serum levels of C4M (p<0.05), a marker of type IV collagen degradation.

Genkyotex will submit this new data for presentation at key international liver conferences.

“These results provide further evidence of the anti-fibrotic activity ofsetanaxib and can explain the marked and rapid reduction in liver stiffness observed in our successful Phase 2 PBC trial. Targeting liver fibrosis is a key therapeutic objective in PBC because advanced liver fibrosis predicts adverse outcomes even in patients who achieve a biochemical response following treatment with anticholestatic agents 1 . Importantly, this new data corroborates our intention to include patients with elevated liver stiffness in an upcoming pivotal Phase 3 trial with setanaxib”, said Philippe Wiesel, M.D., Executive Vice President and Chief Medical Officer at Genkyotex. 

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