A study examining novel gene therapy for the treatment of the bleeding disorder hemophilia B will be presented at the 52nd Annual Meeting of the American Society of Hematology. Hemophilia B is an inherited bleeding disease in which patients lack proteins that enable the blood to clot.
“The results of this study show promise that gene therapy may play a role in helping treat incurable disorders, such as hemophilia B,” said J. Evan Sadler, MD, PhD, current ASH President-Elect, and Professor of Medicine at Washington University School of Medicine, St. Louis.
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]
Hemophilia is a genetic bleeding disorder that prevents the blood from clotting normally, leading to prolonged bleeding after injury or surgery, or occasionally even in the absence of trauma. The two most common types, hemophilia A and hemophilia B, are caused by defective or missing proteins-factor IX in hemophilia B and factor VIII in hemophilia A-that help the blood to clot. Hemophilia B is the rarer of the two types of the disorder, and treatment varies based on the severity of disease. Patients with severe hemophilia B usually need replacement therapy via infusions of factor IX (FIX) to prevent bleeding that could cause permanent damage to joints, muscles, the brain, and other parts of the body.
One ground-breaking treatment approach is to utilize gene therapy-replacing the defective gene that causes the disorder with a correct version. The investigators in this open-label phase I/II clinical trial are testing a unique approach for severe hemophilia B treatment that uses gene therapy methods. They are evaluating three dose levels of a self complementary AAV vector (scAAV) that enables the transfer of a normal gene for FIX, the transgene, to determine which vector dosage can generate therapeutic levels of FIX without causing adverse effects.
Initially, two patients, who had no detectable FIX, received the gene therapy vector by peripheral vein infusion at the low dose without any side effects. The first patient’s FIX levels increased from less than 1 percent to between 1.5 and 2 percent of normal levels within two weeks. This increased level of FIX, which can significantly decrease the risk of bleeding, was maintained for a period of six months following vector infusion. The patient also did not require any treatment with FIX concentrate and did not experienced any spontaneous bleeding. The FIX level of the second patient, who was receiving regular prophylaxis with FIX at the time of intervention, has been maintained at 1 percent, although the patient continued with intermittent preventive treatment, making confirmation of transgene expression difficult. Two additional patients received the vector at the intermediate dosage; preliminary data on these patients will be presented at the ASH annual meeting.
“These early data are highly encouraging that a low dose of this scAAV vector can generate detectable levels of FIX which impact the bleeding phenotype, without any apparent side effects for those patients suffering with severe hemophilia B,” said co-lead study author Andrew M. Davidoff, MD, Member and Chairman of the Department of Surgery at St. Jude Children’s Research Hospital and Professor at the University of Tennessee Health Science Center in Memphis, TN.
Source:
American Society of Hematology