1. Etranacogene dezaparvovec gene therapy was more effective than prophylactic factor IX infusion at reducing annualized bleeding rate amongst patients with moderate-to-severe hemophilia B.
2. Etranacogene dezaparvovec gene therapy effectively increased endogenous factor IX activity in hemophilia B patients, which was stable 18 months after initiating treatment.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Hemophilia B is a genetic coagulation disorder in which the body generates missing or defective clotting factor IX. The implicated X-linked recessive gene can be inherited or a spontaneous mutation. As a result, persons with hemophilia B can struggle with coagulation, bleeding for longer periods of time, or having spontaneous bleeding episodes as compared to their non-hemophilia B counterparts. Typically, treatment for hemophilia B is through infusing factor IX prophylactically through a concentrated factor IX product. However, this process can be burdensome. New gene therapies, such as etranacogene dezaparvovec, have been developed to generate endogenous factor IX amongst those with hemophilia B so that persons with it discontinue factor IX infusions. This study aimed to investigate the effectiveness and safety profile of etranacogene dezaparvovec at reducing bleeding rates amongst adults with moderate to severe hemophilia B when compared against traditional factor IX prophylaxis using a multi-center trial. Results of the study found that this gene therapy was more effective at reducing the annualized bleeding rate compared to factor IX prophylaxis with an acceptable safety profile within the study timeframe of 18 months. However, the long-term effects of this therapy beyond the timeframe of this study remain unclear and further large studies with extensive follow-up are required.
Click to read the study in NEJM
Relevant Reading: Valoctocogene Roxaparvovec Gene Therapy for Hemophilia A
In-Depth [open-label phase 3 clinical trial]: This study was a phase three, non-randomized trial conducted across 33 locations in the United States, European Union, and United Kingdom evaluating the efficacy of gene therapy with etranacogene dezaparvovec at reducing bleeding rate amongst male adults with hemophilia B. Participants were included if their disease was classified as severe or moderately severe with a severe bleeding phenotype. A total of 54 participants were included. Specifically, prophylactic factor IX used in the lead-in period was compared against the post-treatment period after etranacogene dezaparvovec within the same patients. The primary outcome was annualized bleeding rate once factor IX expression was stabilized. Additional outcomes included scores on the International Physical Activity Questionnaire (iPAQ) and EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L), and visual analogue scale (VAS). Results of the study found that the annualized bleeding rate between the lead-in period and post-treatment period decreased after treatment with etranacogene dezaparvovec when compared against factor IX prophylaxis (rate ratio 0.36; 95% Wald Confidence Interval [CI], 0.20 to 0.64; p<0.001). On average, endogenous factor IX activity increased steadily throughout the first six months and steadily maintained until at least 18 months after treatment. However, there were no significant differences observed in the iPAQ and EQ-5D-5L questionnaires. The most common adverse events were arthralgia (33%) and headache (30%). Overall, this study supports the hypothesis that gene therapy with etranacogene dezaparvovec can more effectively reduce the annualized bleeding rate amongst adults with moderate-to-severe hemophilia B when compared against prophylactic factor IX.
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