• Seladelpar maintains potent anti-cholestatic and anti-inflammatory activity and appears safe and well tolerated, with no drug-induced pruritus, through 26 weeks of treatment

• Results support plans for advancing to Phase 3 in the second half of 2018

CymaBay today announced that a late-breaking poster presentation describing new data from a second interim analysis of its ongoing Phase 2 study of seladelpar in patients with primary biliary cholangitis (PBC) will be featured during The International Liver CongressTMhosted by the European Association for the Study of Liver Diseases (EASL) in Paris, France (April 11-15, 2018).  Seladelpar is an orally administered, potent and selective peroxisome proliferator-activated receptor delta (PPARδ) agonist currently in development for PBC and nonalcoholic steatohepatitis (NASH).

These data demonstrate that in patients with PBC, seladelpar exhibits potent and sustained anti-cholestatic and anti-inflammatory efficacy over 26 weeks of administration.  As of January 2018, 71 patients were exposed to at least one dose of seladelpar, of whom 53 received 12 weeks of treatment and 42 received 26 weeks of treatment. At baseline, mean alkaline phosphatase (AP) were 358, 333, and 262 U/L in the 2 mg, 5 mg, and 10 mg groups, respectively. At 12 weeks, changes in AP were -21%, -33%, and -45% in the 2 mg (N=6), 5 mg (N=25), and 10 mg (N=22) groups, respectively. After 12 weeks, dose titration was permitted for patients whose AP remained above normal and at a level where additional AP lowering had the potential to reduce the risk of disease progression. At 26 weeks, decreases in AP were similar across regimens at -45%, -43%, and -43% in the 5 mg (N=13), 5 to 10 mg titration (N=6) and 10 mg (N=19) groups, respectively. At 26 weeks, 69%, 67%, and 79% of patients across these three dose regimens, respectively, had an AP less than 1.67 times the upper limit of normal, with at least a 15% decrease in AP from baseline and normal bilirubin. Overall, 29% of patients had a normal AP at 26 weeks.

Importantly, seladelpar was not associated with drug-induced pruritus. Baseline median pruritus VAS was 10 and 36 in the 5 mg and 10 mg groups, respectively, and patients in the 10 mg group experienced consistent decreases during treatment (-24% at week 26) suggesting potential anti-pruritic activity. Seladelpar was generally safe and well tolerated, with no transaminase elevation safety signal. There were 6 serious adverse events and none were deemed related to seladelpar.

Many companies are developing molecules for NASH (and PBC). The drug that is believed to be in the lead for approval, Ocaliva, has been beset with serious safety issues. A drug with a better safety profile will have significant advantages.