Raptor Pharmaceutical Corp has obtained positive phase-2a clinical trial results from its pilot study of delayed-release cysteamine bitartrate in 11 adolescent patients with non-alcoholic steatohepatitis (NASH), a progressive form of liver disease believed to affect five to 11 per cent of the US population. The results were presented at the Digestive Disease Week 2010 conference in New Orleans, Louisian.

The open-label phase-2a clinical trial was conducted under a collaboration agreement between Raptor and the University of California, San Diego (UC San Diego) at UC San Diego's General Clinical Research Center. Eligible patients with baseline levels of the liver enzymes alanine transaminase (ALT) and aspartate aminotransferase (AST) that were at least twice normal levels were enrolled to receive twice-daily, escalating oral doses of up to 1,000 mg of delayed-release cysteamine bitartrate (a prototype of Raptor's DR Cysteamine) for six months, followed by a six-month post-treatment monitoring period.

Patients showed a marked decline in ALT levels during the treatment period with seven of 11 patients achieving a greater than 50 per cent reduction and 6 of 11 reduced to within normal range. AST levels also saw significant improvements with patients averaging 41 per cent reduction by the end of the treatment phase. The reduction in liver enzymes was largely sustained during the 6 month post-treatment monitoring phase. Other important liver function markers showed positive trends. Levels of cytokeratin 18, a potential marker of disease activity in Non-alcoholic Fatty Liver Disease (NAFLD), decreased by an average of 45 per cent. Adiponectin levels increased by an average of 35 per cent during the treatment period. Reduced adiponectin levels are thought to be a marker of the pathogenesis and progression of NASH. Body Mass Index (BMI) did not change significantly during both the treatment and post-treatment phases. Delayed-release cysteamine bitartrate demonstrated a strong, favourable safety profile, with mean gastrointestinal symptom scores of 1.1 at baseline and 0.7 after six months of treatment using a rating system in which the maximum score of 14 indicates most severe gastrointestinal symptoms.

Joel Lavine, peadiatric gastroenterologist at UC San Diego and principal investigator for the NASH study, said, "While NASH and NAFLD have long been a growing health concern, we have not seen many drugs reach this stage of clinical testing while continuing to show such a favourable safety profile and encouraging efficacy after six months. The trial results are consistent with ALT and AST reductions seen in patients that achieve a 10 per cent weight loss, even though study participants did not show a significant change in body mass index. DR Cysteamine appears to be a promising candidate for further testing in the potential treatment of NASH."

Raptor's chief medical officer, Patrice Rioux, said, "We are very excited about the results of this delayed-release cysteamine bitartrate pilot study in NASH patients. NASH is already an area of significant unmet medical need in adults and with the growing numbers of obese children diagnosed with the disorder, its importance is anticipated to grow rapidly in the coming years. While we are very pleased with the substantial impact seen on liver transaminases, we are particularly encouraged by the rapid drug effect we saw during the early phases of the study as well as the sustained liver enzyme reductions following drug withdrawal. Supported by the long-term safety profile of this compound in cystinosis, this suggests the potential for a longer term, sustainable benefit to overall liver function in NASH patients with DR Cysteamine treatment."

NASH is a more aggressive form of NAFLD, and is the most common cause of chronic liver disease in North America. Although most patients are asymptomatic and feel healthy in early phases of the disease, NASH causes decreased liver function and can lead to cirrhosis, liver failure and end-stage liver disease. While NASH is most common in insulin-resistant obese adults with diabetes and abnormal serum lipid profiles, its prevalence is increasing among juveniles as obesity rates rise within this patient population. There are no currently approved drug therapies for NASH; patients are limited to lifestyle changes such as diet, exercise and weight reduction to manage the disease.

Under a license with UC San Diego, Raptor is developing DR Cysteamine for cystinosis, NASH, Huntington's Disease and other potential therapeutic indications. Cysteamine is known to be a scavenger of reactive oxygen species and potent antioxidant, most likely through its ability to increase intracellular glutathione levels.

Raptor Pharmaceutical Corp is dedicated to speeding the delivery of new treatment options to patients by working to improve existing therapeutics through the application of highly specialized drug targeting platforms and formulation expertise.