At the 50th Anniversary of the Annual Meeting of Society of Toxicology (SOT), Hepregen Corporation announced the successful use of its HepatoPac platform in an in vitro study demonstrating the species-specific liver toxicity of fialuridine (FIAU). The results of the study were presented in a poster session.

Researchers from Hepregen Corporation, in collaboration with Alnylam Pharmaceuticals,investigated the acute and chronic toxicity profiles of FIAU and several analogues in Human and Rat HepatoPac. Using multiple endpoints, FIAU exhibited acute (4 day) and chronic (15 day) dose-dependent toxicity in human HepatoPac. The toxicity was specific to FIAU alone, whereas other nucleoside analogues did not cause toxicity to the same extent. By contrast, Rat Hepatocytes in the HepatoPac platform were not affected by FIAU in the short term and were only mildly impacted chronically, mimicking the species specific in vivo observations.

FIAU, a nucleoside analog that demonstrated promise as an anti-viral therapy, was pulled from clinical trials in 1993 after severe unexpected liver toxicity was observed in patients. No in vitro or in vivo preclinical models predicted the liver liability that was observed in the clinic.

Hepregen Co-Founder and Director of Research, Salman Khetani, Ph.D., commented on the toxicity study, “Traditional in vitro models are very poor predictors of what will be observed in vivo and in the clinic.  This study clearly demonstrates the predictive power of the HepatoPac platform.”

Co-Founder, President and CEO, Bernadette (Bonnie)Fendrock added, “This collaboration is an excellent example where we have been able to demonstrate the significance of Hepregen’s HepatoPac platform. This work combined with validation work from many other companies supports Hepregen’s goal - helping our customers reduce risk and increase confidence in drug development so that they can providethe safest drugs to patients.”

Date: March 9, 2011
Source: Hepregen Corporation