Dr. Spencer Sullivan, Hematologist and Assistant professor of pediatrics at the University of Mississippi Medical Center (UMMC), has presented early trial data on adeno-associated viral (AAV)-mediated gene therapy for Hemophilia B (HB). The results presented at the European Hematology Association’s 21st Congress in Denmark in June 2016, demonstrate the potential of liver-directed gene therapy in treating hemophilia.
HB is a recessive, X-linked, blood clotting hereditary disorder caused by mutations in the gene that code for coagulation factor IX (FIX). It affects about 5,000 men in the United States. The recent success of early-phase clinical trials using AAV-mediated gene therapy have demonstrated the potential of gene therapy in treating HB. However, significant obstacles need to be overcome prior to its widespread adoption. This include immune responses to the AAV capsid and delayed cellular immune response which is vector-dose dependent. To overcome these pitfalls, researchers at UMMC developed a liver-specific AAV vector that could drive therapeutic levels of FIX activity at doses low enough to avoid the need for immunomodulation with steroids. Subjects were infused intravenously with SPK-FIX at a dose of 5 x 1011 vg/kg over a period of ~1 hour.
Preliminary results obtained from the study showed that FIX activity levels plateaued at 28% and 30% respectively at 18 and 7 weeks post infusion for 2 subjects and 16% at 3 weeks post infusion for the third subject. The subjects showed very little or no immune response and no steroids were administered throughout the study. Dr. Sullivan, the study investigator commented: “The patients have experienced no bleeds, no immune response to the treatment and an improved quality of life. This therapy looks like the leading candidate for hemophilia B. This study is a proof of concept that gene therapy is now at the point where we may be able to cure genetic and childhood diseases. An FDA-approved gene therapy for hemophilia is still several years away. The study sites will try different doses and monitor long-term safety and efficacy to ensure that it works. However, the prospects are great.”
Spark and Pfizer Inc. are sponsors of the clinical trial. The next public trial update will be presented during the World Federation of Hemophilia congress in Orlando in July 2016.
Source: FIXing genes: a first at UMMC. Press Release