Calliditas' liver disease trial meets primary endpoint after significant design changes

In recent developments, Calliditas Therapeutics has unveiled positive results for its primary biliary cholangitis (PBC) treatment, although the details of future steps remain unclear. The Swedish biotech company restructured its initial plan for the setanaxib trial, significantly reducing both the scope and duration of the study. Initially set to enroll over 300 patients in a 52-week phase 2b/3 trial, Calliditas later decided to downscale the study. The revised plan involved enrolling only 70 patients, cutting the trial duration to 24 weeks, and switching the primary outcome measure to the reduction in the liver enzyme alkaline phosphatase (ALP).

The changes were made to mitigate research and development costs for the years 2024 and 2025. The recent results, as reported by Calliditas, indicate that the study successfully met its revised primary endpoint. Specifically, the trial compared two different doses of setanaxib to a placebo among 76 PBC patients with elevated liver stiffness. Over 40% of these participants were also taking ursodeoxycholic acid along with either Intercept Pharmaceuticals’ Ocaliva or the PPAR agonist bezafibrate, and 13% were on all three medications simultaneously.

The findings showed that from the baseline, there was a 19% improvement in ALP levels in patients taking the higher dose of setanaxib, and a 14% improvement in those on the lower dose. These changes in ALP, which is typically elevated in PBC patients, were statistically significant when compared to the placebo group at both dosages. The company had previously indicated that liver stiffness and fatigue would be key measures to watch. They reported positive trends in liver stiffness in the phase 2 readout, although the top-line data did not address fatigue.

Regarding safety, setanaxib was generally well tolerated among the participants, with similar rates of treatment-emergent adverse events (TEAEs) in both the placebo and treatment groups. However, there was a higher rate of TEAEs leading to study discontinuation in the setanaxib group compared to the placebo group.

Despite these promising results, the press release from Calliditas did not elaborate on the next steps for setanaxib specifically in the context of PBC. The company did, however, highlight other upcoming studies. A phase 2 trial led by investigators to explore setanaxib for idiopathic pulmonary fibrosis is expected to yield results by the end of the year. Additionally, data from a phase 2 study focused on Alport syndrome is anticipated in 2025.

These studies are part of a broad research and development program that has seen setanaxib tested across various conditions, including head and neck cancer. The extensive nature of this program underscores Calliditas' belief in the potential anti-fibrotic benefits of setanaxib across multiple indications.