Hemophilia B is a rare, X-linked bleeding disorder caused by partial or complete deficiency of clotting factor IX. Currently, the standard of care for these patients is prophylactic intravenous factor IX injections. New results for a phase 3 adeno-associated viral (AAV) gene therapy treatment, however, were recently published in The New England Journal of Medicine. Briefly, 54 adult men with moderate to severe hemophilia B (factor IX activity <2% of the normal value) received a single injection of etranacogene dezaparvovec (AAV5 with high expressing Padua factor IX) and were followed for 18 months. The bleeding rate ratio for post-treatment compared to pre-treatment was 0.36 (p<0.001), and the annualized bleeding rate decreased significantly after treatment from 4.19 to 1.51. Furthermore, 52 patients (96%) did not require further factor IX prophylaxis from 3 weeks to 18 months after treatment. Notably, preexisting AAV5 neutralizing antibodies were detected in 21 patients (38.9%) pre-treatment, but no correlation was observed between pre-existing anti-AAV5 neutralizing antibodies and factor IX activity at 18 months for all but the highest titer of antibody (up to a titer of 678). No adverse events were related to the treatment, but five years of follow-up are planned to fully understand the safety and long-term effects of etranacogene dezaparvovec.
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