NAFLD

Early promise for ASK1 inhibition in NASH

A multicentre, open-label phase II trial (n = 72) evaluated the safety and efficacy of selonsertib, a selective inhibitor of ASK1 (also known as MAP3K5), alone or in combination with simtuzumab (a monoclonal antibody against lysyl oxidase homologue 2) in patients with NASH and moderate to severe liver fibrosis (stage 2 or 3). Alongside liver biopsy, non-invasive imaging methods (magnetic resonance elastography (MRE) and MRI-estimated proton density fat fraction) were used to assess liver stiffness and fat content. After a 24-week treatment period, patients who received selonsertib (6 mg or 18 mg) had higher rates of fibrosis improvement and lower rates of fibrosis progression than those receiving simtuzumab alone. Improvements in fibrosis occurred alongside reduced liver stiffness levels, shown by MRE, and improvement in histological assessments. No difference in adverse events were reported between patient groups.

References

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    Loomba, R. et al. The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: a randomized, phase II trial. Hepatology http://dx.doi.org/10.1002/hep.29514 (2017)

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Ray, K. Early promise for ASK1 inhibition in NASH. Nat Rev Gastroenterol Hepatol 14, 631 (2017). https://doi.org/10.1038/nrgastro.2017.144

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