CymaBay Therapeutics, Inc. announced 12-week topline results from an ongoing 52-week Phase 2b dose-ranging, paired liver biopsy study of seladelpar for the treatment of nonalcoholic steatohepatitis (NASH). Seladelpar is a potent and selective peroxisome proliferator-activated receptor delta (PPARδ) agonist currently in development for NASH and primary biliary cholangitis (PBC).
 
Treatment with seladelpar resulted in minimal reductions in liver fat that were not significant when compared to placebo. Treatment with seladelpar resulted in robust and clinically meaningful reductions in markers associated with liver injury. Alanine aminotransferase (ALT) declined up to 37.5% or 32 U/L in 12 weeks. These reductions in ALT are significantly greater than the 17 U/L threshold that has been correlated with histologic improvement in NASH. 
Gamma glutamyl transferase (GGT) also decreased significantly, suggesting a reduction in hepatocellular oxidative stress. Significant reductions in alkaline phosphatase (AP) at 12 weeks were observed, supportive of a decrease in hepatocellular bile acids. The marked changes in these liver enzymes collectively suggest the potential to impact ballooning and lobular inflammation, the two key components of NASH resolution. Seladelpar demonstrated a favorable safety and tolerability profile at all doses evaluated in this study.
 
Dr. Pol Boudes, MD, Chief Medical Officer of CymaBay Therapeutics, added, “While the reductions in liver fat were minimal, we remain encouraged by the significant improvements in biochemical markers of liver injury that we observed at week 12. The 52-week liver biopsy data will allow us to understand whether the improvement in liver injury markers will translate into histological improvement. The observed improvement in markers of liver injury are consistent with the observed effects of seladelpar in PBC and further support the potential for seladelpar to improve liver health.”