CymaBay's persistence with liver drug pays off as therapy improves biomarkers, itching in phase 3

CymaBay Therapeutics has always believed in its liver disease med seladelpar, even after a 2019 failure in nonalcoholic steatohepatitis (NASH). Now, the drug has shown its mettle in a phase 3 study of patients with primary biliary cholangitis (PBC), teeing up regulatory discussions.

Seladelpar achieved the main and secondary endpoints in the late stage RESPONSE trial by addressing key biomarkers as well as some symptoms associated with the chronic disease. CymaBay said that 61.7% of patients met the primary endpoint with improvement of serum alkaline phosphatase and bilirubin at 12 months compared to 20% of placebo patients.

The anti-cholestatic effect of seladelpar was shown with 25% of patients achieving normalization of alkaline phosphatase at 12 months compared to zero in the placebo arm. Patients also saw a reduction in itch after six months of treatment. Safety was comparable between the treatment and placebo arms, CymaBay said in the Sept. 7 release.

PBC eventually destroys the bile ducts that run throughout the liver, causing damage to the organ. The condition causes incessant itching and can progress to liver transplant.

CymaBay has always believed in seladelpar, even when it failed in NASH in 2019 after biopsies showed signs of liver damage in some patients. With the RESPONSE data in hand, the company now hopes to have what it needs to advance discussions with the FDA and global regulators.

More analyses will be presented from the RESPONSE trial at a future medical meeting, the biotech said. The study featured 193 patients receiving seladelpar or placebo daily.

Seladelpar is an oral selective peroxisome proliferator-activated receptor delta agonist, or delpar, which CymaBay says can regulate critical metabolic and liver disease pathways.

William Blair analyst Andy Hsieh called the latest data on seladelpar a "hat trick" for CymaBay. Hsieh believes the therapy will easily earn an FDA nod with the hit on all endpoints and "will quickly emerge as the best-in-class second-line agent in PBC."

Shares in CymaBay rose just under 8% to $14.90 on the news. "Given the stock’s relatively muted reaction, we are aggressive buyers on the differentiated data," Hsieh wrote.

CymaBay is also testing seladelpar in the phase 3 IDEAL trial, which could broaden the patient base.