Improving Quality of Life Through Gene Therapy for Patients With Hemophilia B

Preliminary data from an ongoing phase I/II trial suggest that patients with hemophilia B produced factor IX (FIX) at sufficient levels after receiving a single infusion of an investigational adeno-associated, virus-mediated gene therapy agent. The therapy, called SPK-9001, uses an inactive virus to deliver FIX into a patient’s cells a small section of DNA that, when stabilized in the patient’s own liver cells, allows the body to produce its own FIX.

Lead author Lindsey A. George, MD, from the Department of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, reported that this trial demonstrated the highest and most consistent levels of FIX production of any gene therapy tested to date.

The SPK-9001 trial enrolled nine adult patients with severe hemophilia B (defined as a baseline FIX expression of <2%); as of the data cutoff point on November 30, 2016, seven patients (age range = 18-52 years; all male) had received infusions of SPK-9001 at a dose of 5×1011 vg/kg. Before infusion, four patients were receiving prophylaxis for bleeding and three patients were being treated on-demand for bleeding; only one patient had a bleeding episode.

These patients reached median FIX expression of >28 percent (range = 12-46%) by 12 weeks post-infusion, resulting in a mean FIX expression of 32.3 percent. These levels approached those seen in healthy adults and “[after a follow-up of 52 weeks] permitted termination of prophylaxis, prevention of bleeding, and nearly complete cessation of factor use,” the researchers reported. Six of the seven patients reported increased physical activity and improved quality of life, determined by the Haemophilia Quality of Life Questionnaire for Adults.

Two participants experienced an autoimmune response to SPK-9001 and were put on corticosteroids. Despite this and a decline in FIX activity level, these two participants have not had any bleeds or required replacement FIX, according to Dr. George. Another participant was infused with FIX concentrate for a suspected ankle bleed two days after vector infusion. The study is ongoing, and the researchers will continue to track patient outcomes for at least five years.

The study is limited by the small population and the heterogeneity among participants.


George LA, Sullivan SK, Giermasz A, et al. SPK-9001: Adeno-associated virus mediated gene transfer for hemophilia B achieves sustained mean factor IX activity levels of >30% without immunosuppression. Abstract #3. Presented at the 2016 ASH Annual Meeting, December 4, 2016; San Diego, California.