Investigators from St Jude Children’s Research Hospital and University College London recently announced extremely encouraging preliminary results of a Phase I/II gene therapy trial in patients with hemophilia B.
Hemophilia B, is a deficiency of Factor IX (FIX), one of the proteins necessary for normal clot formation. The disease affects about 1 in 30,000 people. Without treatment, people with hemophilia B are at risk for uncontrolled, disabling and potentially fatal episodes of both internal and external bleeding.
The FIX gene is carried recessively on the X chromosome, and as a result the disorder, just like hemophilia A (FVIII deficiency), is almost exclusively seen in males, though it is carried by females. Patients with severe hemophilia B, must normally inject themselves intravenously with FIX twice a week.
For such patients, gene therapy offers the enticing prospect of a near normal life, but previous studies have yielded disappointing results.
This study, presented last week at the American Society of Hematology annual meeting, was designed primarily to evaluate the toxicological safety study of low and intermediate doses. Because of the low dose used, researchers anticipated that trial subjects would produce little or no detectable FIX. So it was something of a positive surprise when the first patients FIX levels rose from <1% to 2% of normal, after infusion of the experimental vector.
While this rise, may not sound all that impressive, for a person with hemophilia it means the difference between severe and moderate disease.
Even more surprisingly, the patient’s FIX production remains elevated more than nine months later. Since the infusion the patient has also not suffered any spontaneous joint bleeds or needed prophylactic treatment.
Work on the vector began more than 10 years ago. An adeno-associated virus (AAV) vector known as AAV8 was picked because the incidence of natural infection with AAV8 is low and, like although it targets liver cells it does not integrate into the patient’s DNA. Participants received no immune suppressing drugs prior to infusion of the experimental vector. The results so far suggest the experimental vector does not trigger the T-cell mediated immune response seen in a previous hemophilia B gene therapy trial.
The highest dose of the novel gene-vector combination is scheduled to be infused into the fifth and sixth study participants by mid-January. Investigators will then decide whether to expand the trial to include four more adults with severe hemophilia B.
As always SRxA’s Word on Health will be watching closely and will bring you news of further developments as they are announced.