Baxalta Inc., a wholly-owned subsidiary of Baxter International Inc. (BAX), reported continued progress on the Phase 1/2 open-label clinical trial assessing the safety and optimal dosing level of BAX 335, an investigational factor IX (FIX) gene therapy treatment for hemophilia B, during an oral presentation at the 2015 International Society on Thrombosis and Haemostasis (ISTH) Congress in Toronto, Canada.
Individuals with hemophilia B lack the ability to produce clotting factor IX and are today treated with infusions of plasma-derived or recombinant factor IX. BAX 335 is designed to provide a mechanism for a hemophilia B patient's own liver to begin producing FIX over an extended period following a single dose of treatment.
The technology Baxalta has investigated since 2012 is the Biological Nano Particle (BNP) platform — an advanced rAAV8-based gene therapy technology obtained through the collaboration and subsequent acquisition of Chatham Therapeutics. The BNP platform is designed to enable patients to achieve stable factor IX activity on their own when infused in the body. To achieve a therapeutic effect while keeping vector doses as low as possible, BAX 335 uses FIX-Padua, a naturally occurring, highly active variant of FIX.
A total of seven patients in three sequentially-ascending dosing cohorts have been treated in the trial with evidence of a dose-related response. No patients have developed FIX inhibitors to date. Some FIX expression was observed in the lowest dosing cohort (2x1011 vector genomes [vg] per kilogram of body weight: vg/kg). In the second dosing cohort (1x1012 vg/kg), two patients have experienced no bleeds without regular infusions of FIX and one of these patients has had sustained FIX expression levels of 20-25 percent for 12 months.
In the highest dose cohort (3x1012 vg/kg), expression levels have peaked above 50 percent, though the two patients in this cohort experienced an immune response which has led to decreased FIX expression, with one patient resuming regular FIX infusions. Immune responses have been reported and managed in previous studies with gene therapy technology. Baxalta continues to address the immune responses observed while working to maintain target trough levels.
The clinical trial is assessing the safety of ascending doses of BAX 335 to determine the optimal single dose in up to 16 adult subjects with hemophilia B at treatment centers in the United States. The primary endpoint is the safety of a single dose of BAX 335 administered intravenously. Secondary endpoints include evaluation of the optimal dose to achieve stable therapeutic plasma FIX activity, as well as pharmacokinetics and immune response to treatment.
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