Genkyotex’s (EPA:GKTX) Phase II trial investigating GKT831 for primary biliary cholangitis (PBC) has a positive mechanism rationale for efficacy as its antioxidant and anti-inflammatory effect may have an impact on fibrosis, experts said. However, this comes with the caveat that its targets NOX1/NOX4 are not directly linked to the disease, drawing some expert caution.
The trial’s primary endpoint of change in serum gamma-glutamyltransferase (GGT) may lack clinical value as it can be affected by many other biochemical pathways and thus data noise would have to be expected, experts said. But others noted there is still value in GGT as an efficacy signal since it is matched with GKT831’s mechanism.
However, if GKT831 successfully makes its way to Phase III, debate will continue on its ideal primary endpoint, with some experts noting antifibrotic efficacy is challenging to demonstrate in PBC, with GGT being an unlikely approvable endpoint as it lacks PBC relevance. A future pivotal trial could use Intercept Pharmaceuticals’ (NASDAQ:ICPT) second-line Ocaliva’s (obeticholic acid) alkaline phosphatase (AP) primary endpoint but this may not mirror GKT831’s antifibrotic mechanism, some noted.