Calliditas Therapeutics has announced positive mid-stage results of its NOX enzyme inhibitor for a type of rare liver disease.
The phase 2b TRANSFORM trial has been evaluating setanaxib in 76 patients with primary biliary cholangitis (PBC) and elevated liver stiffness versus placebo.
Estimated to affect approximately 140,000 patients in the US, PBC is a progressive and chronic autoimmune disease of the liver that causes immune injury to biliary epithelial cells, which leads to cholestasis and fibrosis.
The double-blind, randomised trial investigated the effects of setanaxib 1200mg (800mg in the morning and 400mg in the evening) and 1600mg (800mg in the morning and evening) over 24 weeks of treatment.
Granted orphan drug designation by the US Food and Drug Administration for the treatment of Alport syndrome, a genetic condition characterised by kidney disease, loss of hearing and eye abnormalities, in November 2023, the NOX enzyme inhibitor is designed to target specific mechanisms within the body related to oxidative stress and fibrosis.
More than 40% of patients in TRANSFORM were on dual therapy, including UDCA (ursodeoxycholic acid) and either Ocaliva (obeticholic acid) or Bezafibrate as base therapy, and 13% were receiving all three therapies during the study.
Patients treated with setanaxib demonstrated statistically significant improvements in the primary endpoint of alkaline phosphatase of 19% and 14% in the 1600mg arm and the 1200mg arm, respectively, and showed positive trends in liver stiffness assessed by FibroScan at 24 weeks.
Commenting on the results, Renée Aguiar-Lucander, chief executive officer, Calliditas, said: “This positive data provides further clinical evidence of the potential of setanaxib in multiple rare diseases and we are very pleased that we now have additional positive clinical evidence in support of our unique, first-in-class NOX platform.”
The company is also conducting additional clinical trials with setanaxib and expects the phase 2 trial in idiopathic pulmonary fibrosis to provide top-line data by the first quarter of 2025, along with results from the ongoing phase 2 proof-of-concept trial in Alport syndrome.
