About one in four people in North America have non-alcoholic fatty liver disease (NAFLD), in which excess fat accumulates in the liver of an individual who drinks little or no alcohol. NAFLD and its more severe form, non-alcoholic steatohepatitis (NASH), is a top driver of liver disease, including cirrhosis and liver cancer.
NAFLD and NASH often occur with fibrosis, or scarring, of the liver, and yet no medications have been approved to treat such liver damage in this context. In a recent review paper, Joseph J. Alukal, MD, of Mercy Medical Center in Baltimore, and Paul J. Thuluvath, MD, of the University of Maryland School of Medicine, assessed the pipeline for such therapies.
“Early results from some Phase II and Phase III trials are encouraging,” they wrote, “and we believe that therapeutic agents which can halt or improve fibrosis may be available in the near future.”
Indeed, four notable medications that target at least one of the pathways that drive NASH and fibrosis are currently in Phase III trials. The drugs need to achieve the key benchmark of improving fibrosis by one stage without any worsening of NASH.
One such drug, called Ocaliva (obeticholic acid, or OCA), satisfied those key criteria. Another, selonsertib, has yielded disappointing results, while a third, elafibranor, did not meet the criteria but did show promising results among those with more severe cases of NASH. Lastly, the drug cenicriviroc reduced fibrosis among people with NASH and mild to severe fibrosis, with better results among those with worse liver disease at the study’s outset.