Shire’s Investigational Liver Disease Drug Receives Fast Track Designation from FDA


U.S. Food and Drug Administration (FDA) granted Fast Track Designation Status to Shire’s investigational drug, SHP626 (Volixibat) for the treatment of adults suffering from nonalcoholic steatohepatitis (NASH) with liver fibrosis.

shire dublinNASH is a chronic liver disease which presently lacks any approved medicinal treatment. NASH also known as silent liver disease resembles alcoholic liver disease but occurs in patients with no relevant alcohol consumption history. The disease is characterized by presence of fat in the liver which leads to inflammation, damage and ultimately cirrhosis. NASH can be highly severe and may cause diseases such as fibrosis, liver failure, cirrhosis, and liver cancer.

Non Alcoholic steatohepatitis

Figure 1. The spectrum of non-alcoholic fatty liver disease (photo credit: Center for Bioinformatics and Computational Biology, University of Maryland, USA).

SHP626 (Volixibat) is a once  daily, orally administered drug acts as a protein inhibitor and blocks apical sodium dependent bile acid transporter (ASBT).

SHP626 (Volixibat) structure

SHP626 (Volixibat)

ASBT protein helps in recovery of bile acids from GI Tract and return it to liver and helps in the formation of bile in liver from cholesterol. ASBT also regulate plasma lipid and glucose metabolism. Excess of bile acids causes liver damage and affect plasma lipid and glucose level.  ASBT is one of the major factors responsible for NASH.  SHP626 inhibits ASBT thereby reducing the levels of serum bile acid, serum and hepatic cholesterol and plasma glucose.

apical sodium dependent bile acid transporter

Figure 2. Role of ASBT in bile acid cycling (photo credit:

Shire has already completed the preclinical and phase I clinical trials. The trials were conducted to evaluate the safety, tolerability and preliminary activity of the drug in comparison to placebo in healthy as well as overweight and obese volunteers. The trial lacked any serious adverse event other than Diarrhea. Though the drug was discontinued due to one serious adverse event which resulted in elevation of aminotransferase

The company is now preparing phase 2 trials to study the safety, tolerability and efficiency of the drug by varying the drug administration doses in 3 different ranges for 48-weeks in adult patients suffering from NASH. The phase 2 study will be conducted in the U.S., Canada, and United Kingdom.

Philip J. Vickers, Ph.D., head of R&D, Shire said “Shire’s development plan for SHP626 is designed to address the unmet need in the treatment of adult patients who have NASH with liver fibrosis. This Fast Track designation is further recognition of the critical need to develop new, effective therapeutic options for patients with this serious condition.” The FDA Fast Track Designation for SHP626 in NASH was supported by preclinical and phase 1 study. 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.

Featured Image Credit: Bigstockphoto,com

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