Clinical Trials

Calliditas Therapeutics AB has recently announced that the phase 2b TRANSFORM trial met its primary endpoint. The trial showed statistically significant improvement in alkaline phosphatase (ALP) for both doses tested versus placebo. The trial evaluated setanaxib, a NOX enzyme inhibitor, in patients with primary biliary cholangitis (PBC) and elevated liver stiffness.

The TRANSFORM trial is a double-blind, randomised, placebo-controlled phase 2b study investigating the effect of setanaxib 800mg AM + 400mg PM (1,200mg arm), and 800mg BID (1,600mg arm) over 24 weeks of treatment. The basis for the analysis consisted of a data set of 76 patients with PBC and elevated liver stiffness.

Over 40% of the trial population was on dual therapy, receiving UDCA (ursodeoxycholic acid) and either Ocaliva (obeticholic acid) or Bezafibrate (PPAR agonist) as base therapy. Approximately 13% were receiving all three therapies during the study, reflecting that setanaxib has clinically relevant incremental benefit beyond existing standard of care.

Patients treated with setanaxib showed statistically significant improvements in the primary endpoint of ALP of 19% in the 1,600mg arm and 14% in the 1,200mg arm. Setanaxib treatment was generally well-tolerated, with overall number of treatment emergent adverse events (TEAEs) as well as serious TEAEs being similar between active treatment and placebo. The frequency of TEAEs leading to study discontinuation was higher in patients receiving active treatment compared to placebo. Patients also showed positive trends on liver stiffness assessed by FibroScan at 24 weeks.

“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 evsidence in support of our unique, first-in-class NOX platform,” said CEO Renée Aguiar-Lucander.

The company is conducting additional clinical trials with setanaxib and is expecting the investigator-led phase 2 trial in idiopathic pulmonary fibrosis (IPF) to provide top line data in Q4 2024/Q1 2025. Aguiar-Lucander added that: “There is an ongoing phase 2 proof of concept trial in Alport syndrome, which is expected to deliver top line data in 2025. We also look forward to the read out of the investigator led study in IPF as well as the ongoing study in Alport syndrome in due course.”

“It is very encouraging to see a statistically significant treatment effect in this hard-to-treat population which is already on multiple medications in this relatively small study,” said Professor Dave Jones OBE, director of the NHIP Academy, director for Newcastle Centre for Rare Disease, professor of Liver Immunology at Newcastle University, UK.