Comprehensive analysis and prediction of long-term durability of factor IX activity following etranacogene dezaparvovec gene therapy in the treatment of hemophilia B

References

• Srivastava A, Santagostino E, Dougall A, the WFH Guidelines for the Management of Hemophilia panelists and co-authors, et al. WFH guidelines for the management of hemophilia, 3rd edition. Haemophilia. 2020;26(S6):1–158.
   PubMed Web of Science ®Google Scholar
• Buckner TW, Witkop M, Guelcher C, et al. Impact of hemophilia B on quality of life in affected men, women, and caregivers – assessment of patient-reported outcomes in the B-HERO-S study. Eur J Haematol. 2018;100(6):592–602.
   PubMed Web of Science ®Google Scholar
• Batty P, Lillicrap D. Hemophilia gene therapy: Approaching the first licensed product. Hemasphere. 2021;5(3):e540.
   PubMed Web of Science ®Google Scholar
• Von Drygalski A, Giermasz A, Castaman G, et al. Etranacogene dezaparvovec (AMT-061 phase 2b): normal/near normal FIX activity and bleed cessation in hemophilia B. Blood Adv. 2019;3(21):3241–3247.
   PubMed Web of Science ®Google Scholar
• Miesbach W, Meijer K, Coppens M, et al. Gene therapy with adeno-associated virus vector 5–human factor IX in adults with hemophilia B. Blood. 2018;131(9):1022–1031.
   PubMed Web of Science ®Google Scholar
• Gomez E, Giermasz A, Castaman G, et al. Etranacogene dezaparvovec (AAV5-Padua hFIX variant, AMT-061), an enhanced vector for gene transfer in adults with severe or moderate-severe hemophilia B: 2.5 year data from a phase 2b trial. Res Pract Thromb Haemost. 2021;5(Suppl 2):LPB0020.
   Google Scholar
• Miesbach W, Leebeek F, Recht M, et al. Final analysis from the pivotal phase 3 HOPE-B gene therapy trial: Stable steady-state efficacy and safety of etranacogene dezaparvovec in adults with severe or moderately severe hemophilia B. Haemophilia. 2022;28:25–126 (PO143).
   Web of Science ®Google Scholar
• Samelson-Jones BJ, Sullivan SK, Rasko JEJ, et al. Follow-up of more than 5 years in a cohort of patients with hemophilia B treated with fidanacogene elaparvovec adeno-associated virus gene therapy. Blood. 2021;138(Suppl 1):3975.
   Web of Science ®Google Scholar
• Nathwani AC, Reiss U, Tuddenham E, et al. Adeno-associated mediated gene transfer for hemophilia B: 8 year follow up and impact of removing "empty viral particles" on safety and efficacy of gene transfer. Blood. 2018;132(Suppl 1):491.
   Web of Science ®Google Scholar
• Jones HE, Ohlssen DI, Neuenschwander B, et al. Bayesian models for subgroup analysis in clinical trials. Clin Trials. 2011;8(2):129–143.
   PubMed Web of Science ®Google Scholar
• Majowicz A, Ncete N, van Waes F, et al. Seroprevalence of pre-existing nabs against AAV1, 2, 5, 6 and 8 in South african hemophilia a patient population. Blood. 2019;134(Suppl 1):3353.
   Web of Science ®Google Scholar
• Colella P, Ronzitti G, Mingozzi F. Emerging issues in AAV-mediated in vivo gene therapy. Mol Ther Methods Clin Dev. 2018;8:87–104.
   PubMed Web of Science ®Google Scholar
• Gross DA, Tedesco N, Leborgne C, et al. Overcoming the challenges imposed by humoral immunity to AAV vectors to achieve safe and efficient gene transfer in seropositive patients. Front Immunol. 2022;13:857276.
   PubMed Web of Science ®Google Scholar
• Falese L, Sandza K, Yates B, et al. Strategy to detect pre-existing immunity to AAV gene therapy. Gene Ther. 2017;24(12):768–778.
   PubMed Web of Science ®Google Scholar
• Manno C, Pierce G, Arruda V, et al. Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat Med. 2006;12(3):342–347.
   PubMed Web of Science ®Google Scholar
• Nathwani AC, Reiss UM, Tuddenham EGD, et al. Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med. 2014;371(21):1994–2004.
   PubMed Web of Science ®Google Scholar
• George LA, Sullivan SK, Giermasz A, et al. Hemophilia B gene therapy with a high-specific-activity factor IX variant. N Engl J Med. 2017;377(23):2215–2227.
   PubMed Web of Science ®Google Scholar
• Konkle BA, Walsh CE, Escobar MA, et al. BAX 335 hemophilia B gene therapy clinical trial results: Potential impact of CpG sequences on gene expression. Blood. 2021;137(6):763–774.
   PubMed Web of Science ®Google Scholar
• Pipe S, Leebeek FWG, Ferreira V, et al. Clinical considerations for capsid choice in the development of liver-targeted AAV-based gene transfer. Mol Ther Methods Clin Dev. 2019;15:170–178.
   PubMed Web of Science ®Google Scholar
• Mingozzi F, High KA. Immune responses to AAV in clinical trials. Curr Gene Ther. 2007;7(5):316–324.
   PubMed Web of Science ®Google Scholar
• Chowdary P, Shapiro S, Makris M, et al. Phase 1–2 trial of AAVS3 gene therapy in patients with hemophilia B. N Engl J Med. 2022;387(3):237–247.
   PubMed Web of Science ®Google Scholar
• Spiegelhalter DJ, Abrams KR, Myles JP. Bayesian approaches to clinical trials and health-care evaluation: Statistics in practice. 1st ed. Hoboken (NJ): Wiley; 2004.
   Google Scholar
• O'Kelly M, Ratitch B. Clinical trials with missing data: a guide for practitioners (statistics in practice). 1st ed. Hoboken (NJ): Wiley; 2014.
   Google Scholar
• Verbeke G, Molenberghs G. Springer series in statistics: Linear mixed models for longitudinal data. 1st ed. New York (NY): Springer; 2000.
   Google Scholar
• Duncan AW, Dorrell C, Grompe M. Stem cells and liver regeneration. Gastroenterology. 2009;137(2):466–481.
   PubMed Web of Science ®Google Scholar
• Kattenhorn LM, Tipper CH, Stoica L, et al. Adeno-associated virus gene therapy for liver disease. Hum Gene Ther. 2016;27(12):947–961.
   PubMed Web of Science ®Google Scholar
• Berns KI, Muzyczka N. AAV: an overview of unanswered questions. Hum Gene Ther. 2017;28(4):308–313.
   PubMed Web of Science ®Google Scholar
• Ehrhardt A, Xu H, Kay MA. Episomal persistence of recombinant adenoviral vector genomes during the cell cycle in vivo. J Virol. 2003;77(13):7689–7695.
   PubMed Web of Science ®Google Scholar
• Nichols T, Rakhe S, Arruda V, et al. Effect of growth on AAV-mediated expression of FIX-R338L in juvenile hemophilia B dogs. Res Pract Thromb Haemost. 2022;6(Suppl 1):OC 21.4.
   Google Scholar
• Xi M, Makris M, Marcucci M, et al. Inhibitor development in previously treated hemophilia a patients: a systematic review, meta-analysis, and meta-regression. J Thromb Haemost. 2013;11(9):1655–1662.
   PubMed Web of Science ®Google Scholar
• Santoro C, Quintavalle G, Castaman G, et al. Inhibitors in hemophilia B. Semin Thromb Hemost. 2018;44(06):578–589.
   PubMed Web of Science ®Google Scholar
• Miesbach W, Meijer K, Coppens M, et al. Five year data confirms stable FIX expression and sustained reductions in bleeding and factor IX use following AMT-060 gene therapy in adults with severe or moderate-severe hemophilia B. Res Pract Thromb Haemost. 2021;5(Suppl 2):OC 26.3.
   Google Scholar
• Chowdary P, Shapiro S, Makris M, et al. Factor IX expression within the normal range prevents spontaneous bleeds requiring treatment following FLT180a gene therapy in patients with severe hemophilia B: Long-Term follow-up study of the B-Amaze program. Blood. 2021;138(Suppl 1):3967.
   Web of Science ®Google Scholar
• Pasi KJ, Laffan M, Rangarajan S, et al. Persistence of haemostatic response following gene therapy with valoctocogene roxaparvovec in severe haemophilia A. Haemophilia. 2021;27(6):947–956.
   PubMed Web of Science ®Google Scholar
• Pasi KJ, Rangarajan S, Robinson TM, et al. Hemostatic response is maintained for up to 5 years following treatment with valoctocogene roxaparvovec, an AAV5-hFVIII-SQ gene therapy for severe hemophilia A. Res Pract Thromb Haemost. 2021;5(Suppl 2):OC 67.1.
   Google Scholar
• Ozelo MC, Mahlangu J, Pasi KJ, et al. Valoctocogene roxaparvovec gene therapy for hemophilia A. N Engl J Med. 2022;386(11):1013–1025.
   PubMed Web of Science ®Google Scholar
• Visweshwar N, Harrington TJ, Leavitt AD, et al. Updated results of the alta study, a phase 1/2 study of giroctocogene fitelparvovec (PF-07055480/SB-525) gene therapy in adults with severe hemophilia a. Blood. 2021;138(Suppl 1):564.
   Web of Science ®Google Scholar
• George LA, Monahan PE, Eyster ME, et al. Multiyear factor VIII expression after AAV gene transfer for hemophilia A. N Engl J Med. 2021;385(21):1961–1973.
   PubMed Web of Science ®Google Scholar
• Monahan PE, Négrier C, Tarantino M, et al. Emerging immunogenicity and genotoxicity considerations of Adeno-Associated virus vector gene therapy for hemophilia. JCM. 2021;10(11):2471.
   Web of Science ®Google Scholar
• Arruda AR, Samelson-Jones BJ. Gene therapy for immune tolerance induction in hemophilia with inhibitors. J Thromb Haemost. 2016;14(6):1121–1134.
   PubMed Web of Science ®Google Scholar