PB0541 - IX-TEND: A Phase IV Observational, Long-term Follow-up Study on the Safety and Efficacy of Etranacogene Dezaparvovec in Patients with Hemophilia B

Background: Hemophilia B therapy goals include prevention and treatment of spontaneous bleeding episodes, but the current standard-of-care, factor IX (FIX), is not curative. Etranacogene dezaparvovec is an adeno-associated virus type 5 vector containing a highly active FIX Padua transgene approved in the US and Europe. The Phase 3 HOPE-B trial (NCT03569891) in patients with hemophilia B given etranacogene dezaparvovec demonstrated significant reduction in bleeding and FIX consumption with a favorable safety profile; long-term data are needed to assess its durability and safety in a larger population.

Aims: To evaluate the short- and long-term safety and effectiveness of etranacogene dezaparvovec in a larger population of adults with hemophilia B.

Methods: This Phase 4, observational, post-authorization, long-term follow-up, multicenter, international study (NCT06008938) investigates etranacogene dezaparvovec in adults with hemophilia B who have provided informed consent. Two cohorts (each targeting enrollment of n~250) will include patients with hemophilia B given either 1) commercially available etranacogene dezaparvovec as a single intravenous infusion, or 2) FIX prophylaxis while enrolled in the US American Thrombosis and Hemostasis Network Transcends: Natural History Observational Cohort Study or in local registries in other countries (Figure). For both cohorts, patients will be enrolled 5 years from enrollment of the first patient treated post-approval (June 15, 2023) and followed for 15 years. Effectiveness and safety data during and after treatment at predetermined timepoints, as well as medical history, will be collected. Formal hypothesis testing is not planned, hence control for type I error is not required.

Results: Primary and secondary endpoints are summarized (Table). First analysis of results is planned after ~50 patients have completed 1 year follow-up. Final report is expected in 2044.

Conclusion(s): This study will provide long-term data on the effectiveness and safety of etranacogene dezaparvovec and build on its efficacy and safety profile in a larger population.