Non-alcoholic Steatohepatitis (NASH)

What is NASH?

NASH is a progressive form of chronic liver disease that is one of the leading causes of liver cirrhosis in the U.S. NASH constitutes about 10% of newly diagnosed cases of chronic liver disease in the U.S. and affects 2% to 5% of the population. Diagnosis occurs mostly in overweight adults and children, yet NASH can also occur in individuals with normal weight.

Generally, there are no symptoms in the beginning stages of NASH, so testing typically occurs after a blood panel shows elevated liver enzyme levels that cannot be explained by the use of medication or excessive alcohol. NASH is suspected when x-rays or other imaging procedures show excessive fat in the liver. Final diagnosis is made when a liver biopsy confirms inflammation and liver cell damage. NASH can lead to scarring of the liver, cirrhosis and eventually liver failure. This process can take years or even decades, at which point a liver transplant may be necessary.

Current Standard of Care

At the present time, there are no therapies to treat NASH. General lifestyle changes that are recommended to stop progression of the liver disease include:

• Weight loss
• Healthy diet
• Exercise
• Avoidance of alcohol

Research and Development for NASH

Because of its rapidly growing incidence in developed countries, NASH is an area of active research and development by clinicians and pharmaceutical companies. Some studies have shown that reduction of oxidative stress in the liver with anti-oxidants may result in improvements in NASH patients as determined by imaging and liver enzyme measurements (Contos 2002, Franzese 1997, Lavine 2000).

In a Phase 2b clinical trial, Raptor is investigating the use of RP103 delayed-release cysteamine bitartrate capsules for the potential treatment of NASH in juveniles in collaboration with NIDDK, a division of the NIH. Cysteamine, which is readily taken up in the liver, is a precursor of glutathione, a potent liver anti-oxidant.

Raptor’s Phase 2a clinical trial of delayed-release cysteamine bitartrate (a prototype of Raptor’s RP103) showed a marked decline in juvenile NASH patients’ ALT levels during the treatment period with 7 of 11 patients achieving a greater than 50% reduction and 6 of 11 reduced to within normal range. AST levels also saw significant improvements with patients averaging 41% reduction by the end of the treatment phase. The reduction in liver enzymes was largely sustained during the 6 month post-treatment monitoring phase.

Additional Resources

• National Digestive Diseases Information Clearinghouse (NDDIC)
• NIH List of NASH Studies

 

Raptor Collaborates with NIDDK

Raptor signs Collaborative Research and Development Agreement With NIDDK on Phase 2b Clinical Trial of RP103 (delayed release cysteamine bitartrate capsules) in Non-Alcoholic Steatohepatitis (NASH).

Phase 2a Clinical Trial Completed

Raptor presented at the Digestive Disease Week 2010 Conference. Primary endpoints met.