Global biotherapeutics leader CSL Behring announced positive long-term results from the Phase 3 HOPE-B clinical trial evaluating etranacogene dezaparvovec (EtranaDez), an investigational adeno-associated virus five (AAV5)-based gene therapy for people living with hemophilia B, a life-threatening bleeding disorder. Following a single infusion of etranacogene dezaparvovec, participants experienced a stable and durable increase in mean Factor IX (FIX) activity and hemostatic protection at 18 months. The final data, from the largest gene therapy study in hemophilia B, were presented as part of the latest clinical trial results session at the European Association of Haemophilia and Allied Disorders (EAHAD) 2022 Annual Meeting.
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“The final 18-month results from the pivotal HOPE-B study continue to establish the durability of etranacogene dezaparvovec gene therapy, which produced Factor IX levels that remained stable and consistent over the course of the study, while also significantly reducing the rate of annual bleeds after a single infusion,” said Professor Wolfgang Miesbach, Head of the Department of Coagulation Disorders and the Comprehensive Care Centre from the University Hospital of Frankfurt, Germany, and an investigator for the HOPE-B trial. “Hemophilia B, like many other genetic diseases, is an ideal target for gene therapy because the disease stems from a single faulty gene, making its replacement with a fully functional F9 gene a robust therapeutic intervention.”
The Phase 3, open label, single-dose, single arm HOPE-B trial, which included 54 male participants with severe or moderately severe hemophilia B, demonstrated that etranacogene dezaparvovec produced mean FIX activity of 39.0 IU/dL at six months and 36.9 IU/dL at 18 months post infusion. After the six-month lead-in period post-infusion, the adjusted annualized bleeding rate (ABR) (1.51) for all bleeds was reduced by 64 percent (p=0.0002) and all FIX-treated bleeds was reduced by 77 percent (3.65 to 0.83; p<0.0001) over months seven to 18. In addition, 98 percent of subjects treated with a full dose of etranacogene dezaparvovec discontinued use of prophylaxis, with an overall 97 percent reduction in mean unadjusted annualized FIX consumption of 257338.8 IU/yr/participant to 8486.6 IU/yr/participant (from lead-in period to months 13-18).
“While progress in today’s FIX prophylaxis treatments has made meaningful improvements in the lives of people with hemophilia B, many patients remain at risk of serious bleeds and other complications, despite regular, ongoing treatment,” said Steven Pipe, M.D., Professor of Pediatrics and Pathology and Pediatric Medical Director of the Hemophilia and Coagulation Disorders Program at the University of Michigan, and the principal investigator of the HOPE-B trial. “Nearly all patients treated with gene therapy in this study were able to discontinue use of prophylaxis. The treatment was also effective in people who have pre-existing neutralizing antibodies, which would typically disqualify someone from this kind of treatment.”
Etranacogene dezaparvovec is generally well-tolerated with the majority of adverse events (80.4 percent) considered mild. One death resulting from urosepsis and cardiogenic shock in a 77-year-old patient at 65 -weeks following dosing was considered unrelated to treatment by investigators and the company sponsor. A serious adverse event of hepatocellular carcinoma was determined, by independent molecular tumor characterization and vector integration analysis, to be unrelated to treatment with etranacogene dezaparvovec. No inhibitors to FIX were reported.