Novel gene therapy shows promise in hemophilia B

For treatment of hemophilia B (HB), an X-linked bleeding disorder ideally suited for gene therapy, UK and USA researchers report successful use of peripheral vein infusion of a single dose of a serotype-8 pseudotyped self-complementary adeno-associated virus (AAV) vector expressing a codon-optimized coagulation factor IX (FIX) transgene (scAAV2/8-LP1-hFIXco).

Amit Nathwani, MD, PhD, of the Department of Hematology at UCL Cancer Institute in London, co-lead study author, and colleagues enrolled sequentially six severe HB subjects (FIX </=1%) in three dose cohorts with two subjects in each group. Vector was administered without immunosuppression. The subjects were followed for 6-16 months post treatment.

The researchers reported AAV-mediated expression of FIX at 2%-11% of normal in all subjects. Four of the six discontinued prophylaxis and remain free of spontaneous hemorrhage. The other two increased the interval between FIX prophylaxes.

One high-dose subject developed asymptomatic, transient elevation of serum transaminases.  A second high-dose subject had a slight increase in liver enzymes. For both subjects, treatment with a short course of steroids led to rapid normalization of the transaminases and maintenance of FIX levels in the 3%-11% range.