Presentation Highlights

During Tuesday’s State-of-the-Art Session “Novel Therapies for Hemophilia”, President and Chief Scientific Officer of Spark Therapeutics, Katherine High, M.D., Ph.D. summarized findings from their phase I/II trial of the long-term safety and efficacy of factor IX (FIX) gene therapy in patients with hemophilia B.

  • The lowest dose of investigational SPK-9001 vector, 5x1011 vg/kg, was effective at increasing factor IX levels.
  • The first of 10 patients had a factor IX level increase to 33% that was sustained at 18 months; average sustained plateau FIX level was ~30% among all subjects.
  • Two of 10 patients developed an immune response that was resolved with a short course of steroids.
  • As a group, the 10 participants had a 99% reduction in bleeds and a 96% reduction in factor use.
  • Pfizer will take the vector into phase III.

A phase I/II trial of the long-term safety and efficacy of factor IX gene therapy was designed to meet the needs of patients with severe to moderately severe hemophilia B. The goal of gene therapy is to prevent and continuously control bleeding, and to eliminate the peaks and troughs that occur with factor IX replacement therapy.

High provided preliminary data from the first 10 participants of the study. Patients were 18 to 53 years of age and had severe to moderately severe hemophilia B. Seven patients had a factor IX <1%, 3 had baseline levels of 1% to 2%. At the time of study entry, seven participants were maintained on prophylaxis, and three were maintained on on-demand regimens. All 10 patients underwent infusion of SPK-9001 vector at a dose of 5x1011 vg/kg. After the initial observation period, frequent blood draws were done to assess factor activity.

The factor IX variant that was used in this phase I/II trial was naturally-occurring and had high specific activity. The mutant factor IX was identified when a young man presented with thrombosis and was found to have a FIX mutation that resulted in FIX with a marked increase in activity. This information was then used to create a transgene that would deliver increased FIX activity. The trial was designed to be a dose-escalation trial but even at the lowest doses, factor IX levels were adequate to provide hemostasis and dose escalation was not required.

One patient’s factor IX rose to 33% over 10 weeks, and at 18 months post gene transfer the level remained at 33%. No bleeds were observed, and no steroids were required. For the other 9 patients, the mean level of factor IX attained was 30%. Two of 10 patients developed a short-term immune response, manifested by a very modest rise in transaminase levels, which resolved with short course of steroids; 1 of these currently has a factor IX level of 15%, the other is at 79%. All patients had 99% reduction in bleeds and 96% reduction in the use of factor IX replacement therapy. Nine of 10 patients have not required any factor IX replacement therapy.

Pfizer will partner with Spark to develop and complete a phase III trial with this therapeutic strategy.

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