Early phase 2a study results of a combination of the 2 agents previously evaluated as NASH monotherapies led to the FDA award for Pfizer.
Pfizer Inc today was awarded Fast Track designation by the US Food and Drug Administration (FDA) for its investigational combination therapy for the treatment of non-alcoholic steatohepatitis (NASH) with liver fibrosis, according to a company news release.
The 2-drug combination comprises ervogastat, a diacylglycerol O-acyltransferase 2 (DGAT2) inhibitor, and clesacostat, an acetyl-CoA carboxylase (ACC) inhibitor. DGAT2 and ACC are both enzymes that regulate lipid metabolism. Agents that inhibit the enzymes are linked to reduction in liver fat in individuals with nonalcoholic fatty liver disease (NAFLD), according to Pfizer.
“Receiving Fast Track designation from the FDA reinforces Pfizer’s belief in ervogastat/clesacostat as a potential treatment for NASH, a serious, progressive liver disease with no currently approved therapies,” said James Rusnak, MD, PhD, Pfizer senior vice president and chief development officer, internal medicine.
NASH, a progressive form of NAFLD, can lead to complications including cirrhosis, hepatocellular carcinoma, and hepatic failure. NASH is also a risk factor for cardiovascular disease.
The FDA’s decision to grant Fast Track designation rests on results of nonclinical studies and a phase 2a clinical study recently published in Nature Medicine that demonstrated the combination reduced liver fat with a favorable safety and tolerability profile.
Evergostat is the result of continued Pfizer research into a NASH treatment candidate set aside in 2018, according to a report by Fiercebiotech. Clesacostat, shelved in 2020, had already received fast-track designation during Pfizer’s testing of the molecule as monotherapy, the report adds.
Pfizer is currently studying ervogastat/clesacostat in an ongoing Phase 2 clinical trial evaluating the impact of treatment on resolution of NASH or improvement in liver fibrosis as assessed by liver biopsy and expects the study to be complete in 2024, the Pfizer statement says. (NCT04321031)
The study of the combined therapy includes an arm investigating ervogastat as monotherapy, results of which will lay groundwork for a potential phase 3 development program.