Pfizer Granted Approval to Initiate Clinical Trials in China for Two NASH Drug Candidates: PF-06865571 (Ervogastat) and PF-05221304 (Clesacostat)

Text | Baihuawen

On September 17, Pfizer’s two new drugs, PF-06865571 tablets and PF-05221304 tablets, were approved to conduct clinical trials in China. The indications are: as monotherapy and in combination with PF-05221304 for the treatment of adult patients with biopsy-proven non-alcoholic steatohepatitis (NASH) accompanied by stage 2 or 3 fibrosis.

NASH is a progressive liver disease closely associated with metabolic disorders such as obesity, insulin resistance, type 2 diabetes, and hyperlipidemia. It is a leading cause of hepatic fibrosis, cirrhosis, liver failure, hepatocellular carcinoma, and death. Currently, there are no NASH treatments approved by the FDA or EMA.

Ervogastat is a diacylglycerol O-acyltransferase 2 (DGAT2) inhibitor, and clesacostat is an acetyl-CoA carboxylase (ACC) inhibitor. The combination of the two targets key enzymes in the hepatic triglyceride synthesis pathway, showing potential to become a best-in-class therapy.

Pfizer recently disclosed updates on its NASH drug development pipeline at its Investor Day, revealing that the DGAT2 inhibitor ervogastat as monotherapy for the treatment of NASH reduces steatosis and serum triglyceride levels, whereas the ACC inhibitor clesacostat significantly reduces hepatic steatosis and alanine aminotransferase (ALT) levels but increases serum triglyceride levels.

A Phase IIa clinical study investigating the combination regimen of clesacostat and ervigastat demonstrated that this combination reduced hepatic fat levels by 40% in patients, while simultaneously alleviating the elevation in serum triglyceride levels caused by ACC inhibition.

Currently, both Pfizer’s clesacostat monotherapy and the clesacostat/ervigastat combination therapy are in Phase IIb clinical trials.