New Gene Therapy Could Be Safe, Effective for Hemophilia B Patients

A new kind of gene therapy tested in animals could be safe and effective for human patients with hemophilia B, according to a multi-year, ongoing study. In the study, the researchers developed a way to use a lentivirus, which is a large retrovirus, to deliver factor IX genes to the livers of three dogs with naturally occurring hemophilia. The researchers removed the genes involved in viral replication, a process that turned the virus into a vector. They then injected the viral vectors directly into the liver or intravenously, and after more than three years, the dogs experienced zero or one serious bleeding event each year. Before the therapy, the dogs experienced an average of five spontaneous bleeding events that required clinical treatment. And, importantly, the researchers detected no harmful effects. “The result was stunning,” said Timothy Nichols, MD, director of the Francis Owen Blood Research Laboratory at the University of North Carolina School of Medicine and cosenior author of the study’s paper, which was published in Science Translational Medicine. “Just a small amount of new factor IX necessary for proper clotting produced a major reduction in bleeding events.”

With gene therapy, doctors can give hemophilia patients a one-time dose of new clotting genes instead of a lifetime of multiple injections of recombinant factor IX that, until very recently, had to be given several times a week. A new U.S. Food and Drug Administration-approved hemophilia treatment requires only once or twice monthly injections indefinitely. This new gene therapy would involve a single injection and could potentially save money while providing a long-term solution to a lifelong condition. A major potential advantage of it is the use of lentiviral vectors, to which most people do not have antibodies that would reject them and make the therapy less effective. In human clinical studies, approximately 40 percent of the potential participants screened for a different kind of viral vector — called adeno-associated viral (AAV) vectors — have antibodies that preclude them from entering AAV trials for hemophilia gene therapy treatment. Therefore, more people could potentially benefit from the lentivirus gene therapy approach. Lentivirus vectors are so large that they can carry larger loads, namely the factor IX genes that people with hemophilia B lack (an approach that also could be used for hemophilia A where the factor VIII gene is considerably larger).

To further demonstrate the safety of this new hemophilia treatment, the researchers used three different strains of mice that were highly susceptible to developing complications such as malignancies when introduced to lentiviruses. They found no harmful effects, which they attribute to the lentiviral vector making it safe.

Before testing this gene therapy approach in human trials, the researchers hope to increase the potency of the therapy to decrease spontaneous bleeding even more, while also keeping the therapy safe. Before the treatment, the hemophilia dogs had no sign of factor IX production. After, they exhibited between 1 percent and 3 percent of the production found in normal dogs, a slight increase enough to substantially decrease bleed events. However, the researchers think it would be best if they could boost factor IX production to between 5 percent and 10 percent of normal while remaining safe.