Benzinga | Jun 21, 2021 08:05AM EDT

CymaBay Therapeutics Presents Positive PBC Data at the International Liver Congress 2021

CymaBay Therapeutics, Inc. (NASDAQ:CBAY), a clinical-stage biopharmaceutical company focused on developing therapies for liver and other chronic diseases with high unmet need, today announced positive data from its previously completed Phase 2 study and the ENHANCE Phase 3 study of seladelpar in patients with primary biliary cholangitis (PBC). These data are being presented at The International Liver Congress(tm) 2021 of the European Association for the Study of Liver (EASL) which will be held online June 23rd -- 26th.

In a poster presentation titled "Efficacy, safety, and tolerability of seladelpar in patients with compensated liver cirrhosis due to primary biliary cholangitis (PBC): a pooled analysis of phase 2 and phase 3 studies,"1 Stuart C. Gordon MD, Director of Hepatology for Henry Ford Health Systems, will be reporting the results of a pooled analysis of a subset of 39 patients with compensated cirrhosis from an open-label phase 2 study and a placebo (Pbo) controlled phase 3 study (ENHANCE) assessing the efficacy, safety, and tolerability 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. Cirrhosis was diagnosed using liver biopsy, imaging tests, or liver elastography.

Efficacy analyses at 3 months included:

* Composite response defined as alkaline phosphatase (ALP) < 1.67 x upper-limit-normal, ALP decrease of ? 15% and normal total bilirubin

* Percent change from baseline in ALP

* Normalization of ALP levels

* Other measures of liver function

After 3 months, the composite endpoint was met in 50% of patients in the 5 mg and 63% in the 10 mg groups compared to none in Pbo. Levels of total bilirubin, platelets, albumin, and coagulation parameters remained stable. Seladelpar was well tolerated and appeared safe. Three patients with cirrhosis experienced an SAE, all unrelated to seladelpar. Efficacy, tolerability, and safety in patients with compensated cirrhosis were comparable to that of non-cirrhotic patients.

"These findings suggest that seladelpar may provide an effective treatment option for patients with compensated cirrhosis due to PBC," said Dr. Gordon. "In addition, seladelpar treatment appeared to be safe and was well tolerated which is encouraging given the high unmet need that exists in this population. Confirmation of these findings in the ongoing RESPONSE Phase 3 pivotal study would be an important advancement in the treatment of PBC."

A second clinical presentation2 will be delivered by Dr. Aliya Gulamhusein, Assistant Professor and Clinical Investigator at the Toronto Centre for Liver Disease, demonstrating that in 51 PBC patients previously treated with but no longer taking obeticholic acid (OCA) or fibrates, seladelpar appeared to be safe, well tolerated and showed meaningful and dose dependent improvements in liver biochemistry, including in those taking 10 mg seladelpar a 45% reduction in ALP and a 79% composite response rate. In addition, there were no meaningful differences in the effects of seladelpar treatment between those with prior treatment with OCA or fibrates compared to those without prior treatment.

Additionally, a presentation3 by Dr. Paul Watkins, Professor of Medicine at the University of North Carolina Chapel Hill, will highlight the ajudication of suspected drug-induced liver injury (DILI) in non-alcoholic steatohepatitis (NASH) patients using independent blinded review by a panel of pathologists and hepatologists. A comprehensive process of adjudication found no clinical, biochemical or histologic evidence that seladelpar was hepatotoxic. The process included two extensive rounds of blinded randomized review of all biopsies in the study. The panel concluded that there were no specific cases that were suggestive of DILI and the features identified by the study pathologists were present at baseline. The outcome of the pathology review indicates a need for further research into disease-related changes in the portal tracts of the livers of NASH patients. The panel also recommended that future biopsy trials in NASH should use blinded concurrent review of baseline and end of treatment biopsies. The report from the panel was subsequently submitted to the FDA and the FDA lifted the clinical hold on seladelpar across all three indications.

Finally, a preclinical presentation4 will highlight that the combination of seladelpar and CB-0406 in a mouse model of NASH led to substantially greater reductions in fibrosis and NASH than either monotherapy.

Dr. Dennis Kim, Chief Medical Officer of CymaBay Therapeutics, commented, "The positive clinical results highlight the potential for seladelpar to offer PBC patients with different stages of disease and different prior treatment experience an efficacious and safe treatment option. We look forward to gathering additional data in cirrhotic and non-cirrhotic patients with PBC in RESPONSE, our Phase 3 global pivotal study of seladelpar, that is currently recruiting and enrolling patients."