Calliditas Therapeutics’ NOX enzyme inhibitor succeeded in a Phase 2b trial in people with a rare liver disease that features inflammation and injury in the bile ducts.
In the placebo-controlled 76-participant TRANSFORM trial in patients with primary biliary cholangitis and liver stiffness, patients dosed with 1,600 mg setanaxib achieved a 19% reduction in alkaline phosphatase (ALP) levels from baseline at 24 weeks.
Those enrolled in the lower 1,200 mg dose attained a 14% improvement in ALP. Both doses were statistically significant, according to a Friday release, but the company did not share p-values. ALP levels are measured to help diagnose PBC.
According to Calliditas, setanaxib showed clinical benefit on top of standard of care as more than 40% of enrolled patients were taking ursodeoxycholic acid and either Intercept’s Ocaliva or generic bezafibrate at baseline. A further 13% of study participants were taking all three drugs.
The NOX1/4 inhibitor was well-tolerated, with a similar number of side effects seen in the treatment and placebo arms.
Calliditas obtained the rights to setanaxib during its $102 million buyout of French biotech Genkyotex back in 2020. At the time, Calliditas said NOX inhibition could have “broad clinical utility” beyond PBC and treat a range of other diseases that are characterized by fibrosis.
Setanaxib is currently in an investigator-sponsored Phase 2 test in idiopathic pulmonary fibrosis with topline data expected at the end of this year or early 2025. Separately, Calliditas is running a proof-of-concept Phase 2 study of the drug in Alport syndrome, which is set to read out next year.
In 2019, setanaxib failed to show a statistically significant reduction in gamma-glutamyl transpeptidase (GGT) in a Phase 2 trial in PBC, but it did meet the secondary endpoint of ALP reduction. GGT is also used to diagnose PBC patients.
Last month, Ipsen and Genfit’s elafibranor won FDA approval for PBC based on results from a Phase 3 trial that had a cholestasis response primary endpoint. Ocaliva won its approval in 2016 based on liver fibrosis reduction.