CymaBay Continues Development of Seladelpar for Liver Disease as Interim President, CEO Named

Daniela Semedo, PhD avatar

by Daniela Semedo, PhD |

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CymaBay therapy seladelpar

CymaBay Therapeutics has named Sujal Shah as interim president and CEO following the retirement of Harold Van Wart, PhD. Robert Wills, PhD, will serve as executive chairman during this transition phase.

California-based CymaBay is developing the investigative drug seladelpar (MBX-8025), a potent and selective agonist for PPARδ (peroxisome proliferator-activated receptor delta), a nuclear receptor important for lipid transport, storage, and metabolism in the liver and muscles.

Seladelpar is in clinical development as a first-in-class drug to therapeutically address the three lipid disorders linked with mixed dyslipidemia (abnormal lipid levels in the blood), and most of the cardiovascular risk factors that define metabolic syndrome.

Patients with nonalcoholic steatohepatitis (NASH) — inflammation and damage of the liver caused by a buildup of fat — often have dyslipidemia along with other features of metabolic syndrome such as obesity, diabetes mellitus, and hypertension.

The dyslipidemia in NASH is characterized by increased serum triglycerides (a type of fat, known as a lipid); increased small, dense low-density lipoprotein (LDL); and low high-density lipoprotein (HDL) — lipoproteins that carry cholesterol. While the cause of dyslipidemia in NASH is not well understood, researchers consider that it is likely related to an overproduction of LDL particles in the liver and an abnormal clearance of lipoproteins from the blood.

As announced on the company’s website, CymaBay has completed a Phase 2 clinical trial in which seladelpar was studied in two different daily doses in combination with Pfizer’s cholesterol-lowering drug Lipitor (atorvastatin). Patients with moderate obesity who had mixed dyslipidemia were enrolled in the trial, and received the treatment over eight weeks.

Treatment with seladelpar led to reductions in total LDL (approximately 20%) and selective depletion of the small, dense LDL particles. This resulted in an improvement in the LDL particle size profile. People who have predominantly small and dense LDL particles are at greater risk of developing serious conditions (including coronary heart disease).

The company also reported that the treatment decreased patients’ elevated triglycerides by nearly 30% and induced a 12% increase in HDL, known as the good cholesterol. Higher triglyceride levels can lead to permanent liver damage and cirrhosis.

Overall, the treatment with seladelpar improved all lipid and cardiovascular risk parameters without the side effects commonly experienced by patients who take other combination lipid therapies.

“We remain focused on completing the Phase 2 development program for seladelpar in PBC [primary biliary cholangitis] this year where we expect key interim data from our ongoing study in the third quarter,” Shah said in a news release. “Seladelpar is a potent and selective agonist of the nuclear receptor PPARδ that we believe has the potential to significantly advance the treatment of multiple liver diseases, including PBC and nonalcoholic steatohepatitis, or NASH.”

Also, Shah said, CymaBay’s recent partnership with Kowa Pharmaceuticals America “enables the advancement of arhalofenate into Phase 3 studies for patients with gout and allows us to focus now on signing similar deals for rights to this program outside the U.S.”

“I am excited to have the opportunity to lead an exceptional team here at CymaBay and believe that 2017 can be a transformational year for the company,” he said.

Results from CymaBay’s Phase 2b gout study (NCT02063997) demonstrated that arhalofenate can lower the risk of gout attacks (flares).