The Clot Thickens
Haemophilia B is a genetic bleeding disorder, affecting approximately 80,000 males worldwide1, caused by an insufficient or dyfunctional blood clotting protein called factor IX (FIX).
Whereas normal clotting factor activity levels range from >40% to 150% (or IU/dL), individuals with the severe form of haemophilia B have circulating FIX activity levels of <1% of normal and may experience recurrent joint, muscle, and tissue bleeding, and potentially life-threathening bleeds into a critical closed space (such as the brain) 2,3.
Full adherence to FIX protein replacement prophylaxis is effective; however, treatment has not been universally adopted due to the burden of once or twice weekly intravenous infusions4.
This ongoing phase 1/2 study is evaluating the safety and tolerability of a single intravenous infusion of SPK-9001, an investigational gene transfer product, designed to allow the body to produce its own factor IX protein by transferring a functioning factor IX gene into the body 5.
As of today, enrolment completed for the initial dose level and four subjects have been followed for 7 to 26 weeks after a single intravenous infusion with 5x1011 vg/kg of SPK-9001 without the need for immunosuppression.
No product and/or procedure-related serious adverse events (including immune response) have been reported to date and no subjects have required steroids or other medications to suppress the immune system.
As of May 22, subjects 1-4 showed plateau factor IX activity levels of 32, 39, 25, and 27% of normal, respectively.
All four subjects are no longer infusing FIX protein products; one subject treated himself with a FIX infusion for a suspected ankle bleed two days after the gene transfer administration, otherwise, all subjects have been free from bleeding to date.
These results are consistent in terms of kinetics of rise of factor IX, and are well above the threshold of 12% required to reduce the risk of bleeds6.
Based on the recommended trough levels6, factor IX activity levels over 12% of normal are likely to reduce significantly the risk of joint bleeds in patients with haemophilia B7.
1. Srivastava et al., 2012; Giangrande 2005
2. Gringeri A et al., 2014 and Jansen et al., 2009
3. Srivastava et al., 2013 and ISTH-SSC, 2011
4. Srivastava et al., 2013, National Hemophilia Foundation 2007, Roberts and Eberst 1993
5. Clinicaltrials.gov (https://www.clinicaltrials.gov/ct2/show/NCT02484092)
6. den Uijl IEM et al., 2011
7. Madhi A et al., 2015
Presenter: Dr Katherine A High
Affiliation: Children’s Hospital of Philadelphia, USA
Topic: AAV-MEDIATED GENE THERAPY FOR HEMOPHILIA B-EXPRESSION AT THERAPEUTIC LEVELS WITH LOW VECTOR DOSES
Abstract LB771 will be presented by Spencer Sullivan on Saturday, June 11, 2016, 17:30 - 17:40 in Hall H.
About the EHA Annual Congress
Hematology is a specialty that covers everything to do with blood: its origin in the bone marrow, diseases of blood and their treatments. The latest data on research and developments will be presented. The topics range from stem cell physiology and development, to leukemia, lymphoma, myeloma - diagnosis and treatment; red blood cells -, white blood cells- and platelet disorders; thrombosis and bleeding disorders.
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