Calliditas Therapeutics’ slimmed-down, truncated and rethought primary biliary cholangitis (PBC) drug has hit its primary endpoint. But the biotech only saw a positive trend on liver stiffness and reported a higher rate of treatment-related dropouts on the study drug.
The Stockholm-based biotech set out in 2021 to enroll more than 300 patients in a 52-week phase 2b/3 trial. Management rethought the study late last year, dropping the phase 3 part, cutting the enrollment target to 70 and the duration to 24 weeks and clarifying the primary endpoint of a reduction in the liver enzyme ALP. Calliditas had previously said the changes would reduce its R&D costs for the trial for 2024 and 2025.
This morning, Calliditas reported that the study met its primary endpoint. The trial ultimately compared two doses of setanaxib to placebo in 76 patients with PBC and elevated liver stiffness. More than 40% of participants took ursodeoxycholic acid and either Intercept Pharmaceuticals’ Ocaliva or the PPAR agonist bezafibrate during the study. Thirteen percent of subjects were on all three drugs.
From baseline, Calliditas tracked improvements in ALP of 19% on the high dose and 14% on the low dose. The biotech said the changes in ALP, a liver enzyme that is raised in PBC patients, were statistically significant versus placebo at both doses.
Calliditas named liver stiffness and fatigue as the two other measures to look out for on an earnings call in May. The biotech reported “positive trends on liver stiffness” in the phase 2 readout. The top-line data release makes no mention of fatigue.
Setanaxib was generally well tolerated, according to Calliditas, with similar rates of treatment emergent adverse events (TEAEs) in the placebo and treatment cohorts. The frequency of TEAEs leading to study discontinuation was higher in patients receiving setanaxib compared to placebo.
Calliditas’ press release lacks details of the next steps for setanaxib in PBC. The biotech did highlight two upcoming readouts in other indications. A phase 2, investigator-led idiopathic pulmonary fibrosis trial is scheduled to report results around the end of the year. Calliditas’ phase 2 Alport syndrome study is set to deliver data in 2025.
The studies form part of a multifront R&D program that has seen setanaxib tested in a range of settings including head and neck cancer. The breadth of the program reflects Calliditas’ belief that the potential anti-fibrotic effects of setanaxib have applications in a range of indications.