Pfizer's retired NASH drug shown to reduce liver fat, inspiring new faith in the DGAT2 pathway
Nearly two years ago, Pfizer sent a NASH drug to the freezer because it didn’t appear viable long-term. Now, scientists for the pharma giant say the drug reduces liver fat, and a different version of that therapy may yet see daylight as part of a partnership with Novartis.
In a study published in Science Translational Medicine, Pfizer scientists reported that PF-06427878, a DGAT2 inhibitor, reduced fat and lipogenic gene expression in mouse and rat studies. That triggered small clinical trials, where volunteers in the drug arm saw a 31.5% reduction in liver fat after 14 days and minimal adverse effects.
“Our findings highlight DGAT2 inhibition by a small, potent, selective compound as a potential therapeutic approach for the treatment of NASH,” the authors, led by Neeta Amin, wrote.
NASH, or nonalcoholic steatohepatitis, is a disease where fats build up in the liver for any reason other than alcohol consumption and eventually cause inflammation. It often occurs as a byproduct of obesity or diabetes and has become a rapidly growing field in the last few years, with Western diets increasing incidence. Experts project it will soon be the leading cause of liver transplants, and create a market worth up to $35 billion.
That kind of revenue potential has fueled myriad memorandum-of-understandings, including one last October between Pfizer and Novartis. PF-06427878 wasn’t included in that deal but a different DGAT2 inhibitor, PF-06865571, was and is now in Phase I.
A Pfizer spokesperson told FierceBiotech the drug from the Science study was retired because it “had chemical properties not fully optimized for chronic exposure.” But the company’s scientists wrote they see the published results as validation for the DGAT2 approach.
Social image credit: Jeff Rumans