• At 52 weeks, the mean decreases in alkaline phosphatase were -47% and -46% in the 5/10 and 10 mg groups
• After 26 weeks, the median changes in the pruritus visual analog scale (VAS) was -50% and -55% in the 5 /10 and 10 mg groups
• The company has ongoing Ph IIb trials of seladelpar in NASH

CymaBay Therapeutics, Inc. (NASDAQ: CBAY) presented data from its ongoing Phase 2 study of seladelpar in patients with primary biliary cholangitis (PBC). Presentations were delivered during two late-breaking presentations on 11/12/18 at The Liver Meeting 2018 hosted by the American Association for the Study of Liver Diseases, as well as multiple additional clinical and pre-clinical presentations.  Seladelpar is an orally administered, potent and selective peroxisome proliferator-activated receptor delta (PPARδ) agonist currently in development for PBC and nonalcoholic steatohepatitis (NASH).

Efficacy data  was presented on the first set of patients treated for 52 weeks and safety data on patients that received at least one dose of seladelpar in the ongoing open label Phase 2 PBC study. Eligible PBC patients with either an inadequate response, defined as alkaline phosphatase (AP) greater than 1.67 times the upper limit of normal (ULN), or intolerance to ursodeoxycholic acid (UDCA) were randomized to daily seladelpar at 5 or 10 mg. After 12 weeks, patients on 5 mg could escalate to 10 mg if their AP treatment goal was not met (5/10 mg group). The primary efficacy outcome was the AP % change from baseline.

At 52 weeks, the mean decreases in AP were -47% and -46% in the 5/10 and 10 mg groups, respectively. A key secondary outcome was the composite responder rate measured at week 52 where a responder was defined as a patient with AP <1.67 x ULN, ≥15% decrease in AP, and total bilirubin ≤ULN. At 52 weeks, 59% and 71% of patients met the composite endpoint in the 5/10 and 10 mg groups, respectively. This composite responder rate is the primary endpoint in the global ENHANCE Phase 3 registration study that was recently initiated. The anti-cholestatic effect of seladelpar was further substantiated with normalization of AP levels at 52 weeks in 24% and 29% of patients in the 5/10 and 10 mg groups, respectively. Treatment with seladelpar also demonstrated a robust anti-inflammatory activity with median transaminase decreases of -31% and -33% in the 5/10 and 10 mg groups, respectively. Seladelpar appeared safe and well tolerated.

Of the 119 patients that received at least one dose of seladelpar, 11 serious adverse events were documented and none were considered related to seladelpar. Three patients discontinued seladelpar, of which only one discontinuation, for a grade 1 gastroesophageal reflux, was deemed related to seladelpar. There was no transaminase safety signal, and importantly, there was no indication that seladelpar was associated with drug-induced pruritus.

In a second late-breaking presentation, Dr. Andreas Kremer, MD, PhD, MHBA, Hepatology Department, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, Germany, shared a 26-week analysis from the study on the effect of seladelpar on pruritus. Pruritus is a common clinical symptom of PBC that adversely effects a patient’s quality of life. Twenty-six weeks represents the time point used to evaluate pruritus as a key secondary outcome in the upcoming ENHANCE Phase 3 registration study. After 26 weeks, the median changes in the pruritus visual analog scale (VAS) was -50% and -55% in the 5 /10 and 10 mg groups, respectively. These data suggest that seladelpar is not associated with drug-induced pruritus and support further evaluation of seladelpar’s potential benefit on pruritus.

Dr. Pol Boudes, Chief Medical Officer of CymaBay Therapeutics commented, “We are very encouraged by the clinically meaningful anti-cholestatic and anti-inflammatory effects we continue to see in PBC patients, now with treatment extended through 52 weeks. We believe these results help to de-risk the seladelpar ENHANCE Phase 3 registration study. Phase 3 studies were initiated in  October of this year. The company is currently conducting Phase 2b studies of seleadalpar in NASH.