CymaBay announces results from Phase 2 seladelpar study at ILC

CymaBay announced results from its Phase 2 study of seladelpar in a subset of cirrhotic patients with primary biliary cholangitis, or PBC. These data are being presented at The International Liver Congress, or ILC, along with three other seladelpar clinical and preclinical presentations. Seladelpar is a potent and selective peroxisome proliferator-activated receptor delta, or PPARd, agonist currently in development for PBC and nonalcoholic steatohepatitis, or NASH. The company will be reporting the results of a subset of patients with compensated cirrhosis from an ongoing Phase 2 study designed to assess the safety and efficacy of seladelpar at a daily dose of 5 mg or 10 mg in PBC patients who had an inadequate response or an intolerance to ursodiol and a total bilirubin. Cirrhosis was diagnosed using liver biopsy, liver elastography or liver imaging. Patients initiated on 5 mg could be dose-escalated to 10 mg after 12 weeks of treatment if it was tolerated and AP threshold criterion was not met. The primary outcome was percent change from baseline in AP. Secondary outcome measures included ALT, total bilirubin, and pruritus using the visual analogue scale. At 52 weeks in patients with cirrhosis, mean relative decreases in AP were -36% and -43% in the 5/10 mg and 10 mg group, respectively. Treatment with seladelpar also demonstrated anti-inflammatory activity with a decrease in ALT comparable to what was observed in non-cirrhotic patients. Total bilirubin remained stable throughout 52 weeks. Seladelpar was well tolerated and appeared safe. Three patients with cirrhosis experienced an SAE, all unrelated to seladelpar. Total bilirubin, platelets, albumin, and INR remained stable. No liver decompensation events were observed. There was no transaminase safety signal, and seladelpar treatment was not associated with drug-induced pruritus or hepatotoxicity. A second clinical presentation demonstrates that single dose oral administration of seladelpar was well tolerated and appeared safe in subjects with varying degrees of hepatic impairment and thus provided important information on seladelpar pharmacokinetic exposure and implications for dosing in this population. Additionally, a presentation using the validated GLOBE score to model PBC clinical progression suggests that seladelpar treatment has the potential to be associated with long-term improvement in disease progression. Finally, a preclinical presentation highlights that seladelpar demonstrated substantial anti-fibrotic and anti-steatotic activity in an obese mouse model of NASH.
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