Early Clinical Trial Results Following Administration of a Low Dose of a Novel Self Complementary Adeno Associated Viral Vector Encoding Human Factor IX In Two Subjects with Severe Hemophilia B

Abstract 248 We have developed a unique approach for the treatment of hemophilia B (HB) that is currently being tested in the clinic. This open-label Phase I/II clinical trial entails peripheral vein administration of a single dose of our novel self complementary AAV vector encoding a codon-optimised human FIX transgene (scAAV2/8-LP1-hFIXco) into adult subjects with severe HB. Our plan is to evaluate three dose levels, progressing to the intermediate and high doses only in the absence of toxicity in a minimum of two subjects each. Vector is being administered in the absence of immunosuppression. Thus far, two subjects have received peripheral vein infusion at the low dose, each without any side effects. Importantly, there were no adverse reactions during vector infusion and no subsequent evidence of hepatotoxicity. Overall, there were no significant changes in the complete blood count and serum chemistry panel. The longest follow-up is in the first subject, in whom plasma FIX levels increased from a baseline of Disclosures: High: Genzyme, Inc: Consultancy, Patents & Royalties; Third Rock Ventures: Consultancy; Novo-Nordisk: Consultancy; Shire, Inc.: Consultancy.