Investigational NASH Treatment Volixibat Receives FDA Fast-Track Designation

Drug aims to treat adults with nonalcoholic steatohepatitis with liver fibrosis

The FDA has granted fast-track designation to SHP626 (volixibat, Shire) as an investigational treatment of adults who have nonalcoholic steatohepatitis (NASH) with liver fibrosis.

Shire is developing SHP626 as a once-daily, orally administered inhibitor of the apical sodium-dependent bile acid transporter (ASBT), a protein that is primarily responsible for recycling bile acids from the intestine to the liver. NASH is a serious, chronic liver disease for which there are no approved drugs.

The FDA’s fast-track designation for SHP626 in NASH was supported by preclinical and phase 1 studies. The FDA’s fast track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. However, it does not guarantee that the FDA will ultimately approve SHP626 for NASH or the timing of any such approval.

Shire will initiate its phase 2 trial with SHP626 as a randomized, placebo-controlled, double-blind study to evaluate the safety, tolerability, and efficacy of three doses of volixibat over 48 weeks in adult patients with NASH. The phase 2 study will be conducted in the U.S., Canada, and the United Kingdom.

In preclinical and phase 1 studies, the safety, tolerability, and preliminary activity of SHP626 compared to placebo in healthy volunteers, as well as in overweight and obese volunteers, was assessed. The most common adverse events occurring in the phase 1 trials were gastrointestinal in nature, predominantly diarrhea. While this occurred in most patients, it was not considered serious. Alanine aminotransferase elevation, a serious adverse event determined to be related to the drug, was reported in one patient, which led to the discontinuation of treatment.

NASH is a type of nonalcoholic fatty liver disease characterized by inflammation and the accumulation of fat in the liver. It can be severe and lead to fibrosis, cirrhosis, liver failure, and liver cancer. There is a steady rise in the prevalence of NASH in the U.S. and globally, and the disease is typically associated with obesity, type-2 diabetes, hypertension, and high cholesterol and triglycerides. NASH is the second leading cause of liver transplantation in U.S. adults and is projected to become the leading cause for liver transplantation if the current trajectory continues.

Source: Shire; July 29, 2016.