Bezafibrate

Calliditas Therapeutics’ press release lacks details of the next steps for setanaxib in primary biliary cholangitis. Calliditas Therapeutics’ slimmed-down, truncated and rethought primary biliary cholangitis (PBC) drug has hit its primary endpoint. But the biotech, which changed the midphase trial to cut costs, 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 switching the primary endpoint to reduction in the liver enzyme ALP. Calliditas made the changes to reduce its R&D costs for the trial for 2024 and 2025.This morning, Calliditas reported that the study met its revised 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. 

STOCKHOLM, July 26, 2024 /PRNewswire/ -- Calliditas Therapeutics AB (NASDAQ: CALT) (STOCKHOLM: CALTX) ("Calliditas") today announced that the Phase 2b TRANSFORM trial met its primary endpoint, showing statistically significant improvement in ALP (Alkaline Phosphatase) 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, randomized, placebo-controlled Phase 2b study investigating the effect of setanaxib 800 mg AM + 400 mg PM, ("1200 mg arm") and 800 mg BID ("1600 mg arm") over 24 weeks of treatment. The basis for the analysis consisted of a dataset of 76 patients with primary biliary cholangitis (PBC) and elevated liver stiffness. The treatment groups were relatively well-balanced with no clinically relevant differences between the groups observed at baseline. The result is particularly encouraging as over 40% of the trial population was on dual therapy, ie was receiving UDCA (ursodeoxycholic acid) and either Ocaliva (obeticholic acid) or Bezafibrate (PPAR agonist) as base therapy and 13% were receiving all three therapies during the study, reflecting setanaxib having 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 1600mg arm and 14% in the 1200mg arm and showed positive trends on liver stiffness assessed by FibroScan® at 24 weeks. Setanaxib treatment was generally well tolerated with overall number of TEAEs (treatment emergent adverse events), 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. "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, NHIP Academy; Director, Newcastle Centre for Rare Disease; Professor of Liver Immunology, Newcastle University; and Honorary Consultant Hepatologist, Newcastle upon Tyne Hospitals. "These positive data provide 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. 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," said CEO Renée Aguiar-Lucander. "I am delighted that we have seen statistically significant and clinically meaningful improvements in ALP with encouraging trends in other outcomes in this population of patients with PBC. I'd like to extend my thanks to investigators, clinical trial site staff, and most importantly patients, who have all contributed to this important study," said CMO Richard Philipson. The company is conducting additional clinical trials with setanaxib and is expecting the investigator led Phase 2 trial in IPF (idiopathic pulmonary fibrosis) to provide top line data in Q4 2024 / Q1, 2025. There is also an ongoing Phase 2 proof of concept trial in Alport syndrome, which is expected to deliver top line data in 2025. For further information, please contact: Åsa Hillsten, Head of IR & Sustainability, Calliditas Tel.: +46 76 403 35 43, Email: [email protected] The information was sent for publication, through the agency of the contact persons set out above, on July 26, 2024 at 08:00 a.m. CET. This information was brought to you by Cision The following files are available for download: