CymaBay Therapeutics has reported positive data from the Phase III clinical trial of seladelpar in patients with primary biliary cholangitis (PBC).
Seladelpar is a selective agonist of peroxisome proliferator-activated receptor delta (PPARδ). It has shown anti-cholestatic and anti-inflammatory properties in clinical studies for PBC.
Named ENHANCE, the double-blind, placebo-controlled, randomised, global Phase III trial assessed a 5mg and 10mg once-daily dose of the drug in a total of 265 patients.
The primary outcome was the responder rate determined as an alkaline phosphatase (ALP) level < 1.67 x the upper limit of normal (ULN) with at least a 15% reduction from baseline and a normal total bilirubin level after 52 weeks.
As the study was stopped early and a small number of patients reached the 52 week timepoint, the primary outcome was updated to a three-month timepoint that was achieved by 167 of 265 patients.
Seladelpar met the primary composite outcome, demonstrating high statistical significance in 78.2% of participants treated with the 10mg dose and 57.1% in the 5mg group versus 12.5% of those who received placebo after three months.
Mean decreases of 38%, 30%, and 2% in ALP were reported in the 10mg, 5mg and placebo groups, respectively.
The drug also led to a strong, dose-dependent decrease in pruritus following three months of treatment in patients with an NRS ≥4 compared to placebo. Anti-inflammatory activity of the drug was also reported at three months.
Seladelpar showed a favourable safety and tolerability profile during the trial, with the adverse events being similar across the seladelpar and placebo groups. No grade 3 or higher ALT elevations were found.
CymaBay Therapeutics CEO and president Sujal Shah said: “These results confirm what was observed in our Phase II open-label study and serve to reinforce our confidence in developing seladelpar as a new therapy addressing the key unmet needs for patients as we re-initiate a Phase III registration study in PBC.”
In November last year, the company announced the termination of Phase IIb and Phase II trials of seladelpar in non-alcoholic steatohepatitis (NASH) and primary sclerosing cholangitis (PSC), respectively.
The decision was based on biopsy findings, which showed liver damage in some NASH patients in the Phase IIb study.