RARE Daily

CymaBay Reports Positive Results for Seladelpar in Patients with Primary Biliary Cholangitis

August 3, 2020

Rare Daily Staff

CymaBay Therapeutics reported positive topline results from the phase 3 ENHANCE study of seladelpar for the treatment of primary biliary cholangitis that demonstrated it to be efficacious, safe, and well tolerated.

The data were reported just one week after the U.S. Food and Drug Administration lifted a clinical hold on seladelpar, which was in clinical development for three liver disease indications including two rare diseases: primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), as well as nonalcoholic steatohepatitis (NASH).

PBC is a rare condition that causes the bile ducts in the liver to become inflamed, damaged, and destroyed. This causes bile, a fluid that helps in digestion, to build up in the liver. This build-up damages the liver over time, eventually causing it to lose its ability to function.

Seladelpar is a potent, selective, orally active PPARδ agonist that is in development for the treatment of the liver diseases with the lead indication being PBC. For PBC, The FDA and the European Medicine Agency granted seladelpar an orphan designation. Seladelpar also received Breakthrough Therapy designation from the FDA and PRIority MEdicine status from the EMA for PBC.

“Although ENHANCE was terminated prior to completion of the 52-week treatment period, topline data for patients through 12 and 26 weeks of treatment demonstrate robust anti-cholestatic, anti-inflammatory and anti-pruritic activity of seladelpar,” said Sujal Shah, president and CEO of CymaBay. “These results confirm what was observed in our phase 2 open-label study and serve to reinforce our confidence in developing seladelpar as a new therapy addressing the key unmet needs for patients as we re-initiate a phase 3 registration study in PBC.”

ENHANCE was a double-blind, placebo-controlled, global study that randomized 265 PBC patients to placebo, seladelpar 5 mg, or seladelpar 10 mg once daily. Due to the early termination of the study and the small number of patients who had reached the 52 week time point, the primary outcome measure was amended prior to database lock to a three month time point which was reached by 167 of 265 patients.

Seladelpar achieved the primary outcome, a composite measure of liver function, with high statistical significance in 78.2 percent of patients in the 10 mg group (n=55) and 57.1 percent in the 5 mg group (n=56) compared to 12.5 percent on placebo (n=56) after 3 months. Rapid, dose-dependent reductions in the liver enzyme ALP were observed as early as one month in seladelpar treated patients with mean decreases of more than 30 percent in the treated patients compared to 2 percent in the placebo group. The anti-cholestatic effect of seladelpar was further substantiated with normalization of ALP levels at 3 months in 27.3 percent of patients in the 10 mg group compared to zero in the placebo group. A similar pattern was achieved in these endpoints at 6 months but with smaller numbers of patients reaching this point in the study.

“The results presented are exciting and are a cause for optimism for patients living with PBC,” said Gideon Hirschfield, professor at the University of Toronto. “Data from this study show that seladelpar appears safe and well tolerated and the efficacy demonstrated points to the potential for seladelpar to be a best-in-class treatment alternative for patients with PBC.”

CymaBay plans to start a 52-week study of seladelpar in PBC in order to support a marketing application to the FDA.

Photo: Sujal Shah, president and CEO of CymaBay


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