Tysabri: genotox, carcinogenicity and repro: done or skipped?

“There were no indications for a mutagenic potential as expected for a protein-like monoclonal antibody nor for potential contaminants or product excipients in the drug product.”

“Standard short or long term carcinogenicity studies were not performed due to the proteinous nature of the test article. Two in vitro and three in vivo studies were performed to study the effects the natalizumab on human α 4 expressing tumour cell lines in vitro and in vivo (as transplants into SCID and nude mice).”

“Natalizumab treatment at 30 mg/kg resulted in a significant reduction (approx 50%) in pregnancy rates, an effect that was not seen at 0; 3 or 10 mg/kg.”

“Decreases in systemic and left ventricular pressures with associated decreases in ventricular contractile indices were seen in one dog treated with 3 mg/kg and two dogs treated with 30 mg/kg natalizumab.”