OR11
Durable bleed protection for all bleeding subtypes and favorable safety over 5 years (end-of-study) in the Phase 3 HOPE-B trial for persons with severe or moderately severe Haemophilia B
F. W. G. Leebeek1,*, W. Miesbach2, M. Recht3,4, N. S. Key5, G. Castaman6, S. Lattimore7, M. Coppens8,9, N. O’Connell10, S. Le Quellec11, N. W. D. Jansen11, F. Wang11, D. Drelich11, P. E. Monahan11, S. W. Pipe12 on behalf of all HOPE-B investigators
1Erasmus University Medical Center Rotterdam, Rotterdam, Netherlands, 2University Hospital Frankfurt, Frankfurt, Germany, 3Yale School of Medicine, New Haven, CT, 4National Bleeding Disorders Foundation, New York, NY, 5University of North Carolina, Chapel Hill, NC, United States, 6Center for Bleeding Disorders and Coagulation, Department of Heart, Lungs, and Vessels, Careggi University Hospital, Florence, Italy, 7Oregon Heath & Science University, Portland, OR, United States, 8Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, 9Amsterdam Cardiovascular Sciences, Pulmonary Hypertension & Thrombosis, Amsterdam, Netherlands, 10National Coagulation Centre, St. James's Hospital; School of Medicine, Trinity College, Dublin, Ireland, 11CSL Behring, King of Prussia, PA, 12Departments of Pediatrics and Pathology, University of Michigan, Ann Arbor, MI, United States
Introduction: Etranacogene Dezaparvovec (CSL222, Hemgenix®) is the first and only approved gene therapy for Hemophilia B (HB) in people with and without pre-existing neutralizing antibodies to adeno-associated virus serotype 5 (AAV5). The pivotal HOPE-B trial (NCT03569891) demonstrated superior bleed protection of etranacogene dezaparvovec (an AAV5 vector containing factor IX [FIX] Padua transgene) compared to FIX prophylaxis over 4 years of post-treatment follow-up. This analysis focuses on FIX-treated bleeds over 5 years post-treatment (HOPE-B end-of-study).
Methods: 54 adult male participants with severe or moderately severe HB (FIX ≤2 IU/dL) received etranacogene dezaparvovec following a ≥6-month lead-in period of their usual FIX prophylaxis. Adjusted annualized bleeding rates (ABR) for FIX-treated bleeds, FIX consumption, and safety up to 5 years post-treatment are reported.
Results: Mean (SD) endogenous FIX activity (IU/dL) was 39.0 (18.7) at month 6 (n=51) and maintained at 36.1 (15.7) at year 5 (n=48) post-treatment. Mean adjusted ABR for all FIX-treated bleeds was reduced from 3.61 in the lead-in period to 1.25 (p=0.0190) during the entire post-dose period and was <1 for each of the 5 years post-treatment (Table 1). A sustained reduction throughout 5 years of follow-up was observed for mean adjusted ABRs in each subtype of FIX-treated bleeds - spontaneous, traumatic, and joint bleeds - (Table 1), and was <0.5 for each of the 5 years post-treatment. FIX consumption (excluding surgery) was reduced by 96%, and 94% of participants remained free of prophylaxis. No long-term hepatotoxicity or AAV-related oncogenicity was observed.
Discussion/Conclusion: Five-year HOPE-B trial follow-up demonstrated lasting efficacy, including a sustained reduction in FIX-treated bleeds, and a favorable safety profile. Consenting HOPE-B participants will be monitored long-term for a total of 15 years post-treatment in the IX-TEND 3003 study (NCT05962398).
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Disclosure of Interest: F. Leebeek Grant/Research support from: CSL Behring, Takeda, and Sobi, Consultant for: CSL, Biomarin and Takeda, of which the fees go to the institution, W. Miesbach Consultant for: Bayer, Biomarin, Biotest, CSL Behring, Chugai, Freeline, LFB, Novo Nordisk, Octapharma, Pfizer, Roche, Sanofi, Takeda/Shire, and uniQure, M. Recht Speaker Bureau of: Board of Directors for Partners in Bleeding Disorders, N. Key Consultant for: Novo Nordisk AS, and has served on Scientific Advisory Committees for Expression Therapeutics and Centessa, G. Castaman Consultant for: Roche, uniQure, Biomarin, CSL Behring and Novo Nordisk; and advisory boards/speaker fees from Bayer, Bioviiix, Takeda, SOBI, Novo Nordisk, LFB, Kedrion, Octapharma, Werfen, Roche, Sanofi, and Pfizer, S. Lattimore: None declared, M. Coppens Grant/Research support from: Bayer, CSL Behring, Novo Nordisk, and F. Hoffman-La Roche, and honoraria for lecturing or consultancy from Alexion/AstraZeneca, CSL Behring, Octapharma, Pfizer, Regeneron, Sobi, and Spark Therapeutics. Non-financial conflicts of interest: member of the gene therapy working group of the European Association for Haemophilia and Allied Disorders (EAHAD), Member of the European Reference Network (ERN) EuroBloodNet, N. O’Connell Grant/Research support from: Sobi, Consultant for: F. Hoffmann-La Roche Ltd, uniQure, Sobi, and CSL Behring, Speaker Bureau of: F. Hoffmann-La Roche Ltd, Sobi, CSL Behring, Takeda, Bayer, and Novo Nordisk. All fees are donated to an institutional charitable body that supports education in hemostasis and thrombosis, S. Le Quellec Employee of: CSL Behring, N. Jansen Employee of: CSL Behring, F. Wang Employee of: CSL Behring, D. Drelich Employee of: CSL Behring, P. Monahan Employee of: CSL Behring, S. Pipe Consultant for: Bayer, BioMarin, CSL Behring, HEMA Biologics, Inovio, LFB, Metagenomi, Novo Nordisk, Pfizer, Poseida Therapeutics, Roche/Genentech, Sanofi, Takeda, Spark Therapeutics and Star Therapeutics, and holds a membership on a Scientific advisory committee for GeneVentiv and Equilibra Bioscience.