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Gene Therapy with E...
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Pipe, Steven W.University of Michigan
(author)
Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B
- Article/chapterEnglish2023
Publisher, publication year, extent ...
Numbers
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LIBRIS-ID:oai:lup.lub.lu.se:9523cf94-85cb-478e-b63b-08992dc1c4aa
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https://lup.lub.lu.se/record/9523cf94-85cb-478e-b63b-08992dc1c4aaURI
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https://doi.org/10.1056/NEJMoa2211644DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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Background: Moderate-to-severe hemophilia B is treated with lifelong, continuous coagulation factor IX replacement to prevent bleeding. Gene therapy for hemophilia B aims to establish sustained factor IX activity, thereby protecting against bleeding without burdensome factor IX replacement. Methods: In this open-label, phase 3 study, after a lead-in period (≥6 months) of factor IX prophylaxis, we administered one infusion of adeno-associated virus 5 (AAV5) vector expressing the Padua factor IX variant (etranacogene dezaparvovec; 2×1013 genome copies per kilogram of body weight) to 54 men with hemophilia B (factor IX activity ≤2% of the normal value) regardless of preexisting AAV5 neutralizing antibodies. The primary end point was the annualized bleeding rate, evaluated in a noninferiority analysis comparing the rate during months 7 through 18 after etranacogene dezaparvovec treatment with the rate during the lead-in period. Noninferiority of etranacogene dezaparvovec was defined as an upper limit of the two-sided 95% Wald confidence interval of the annualized bleeding rate ratio that was less than the noninferiority margin of 1.8. Superiority, additional efficacy measures, and safety were also assessed. Results: The annualized bleeding rate decreased from 4.19 (95% confidence interval [CI], 3.22 to 5.45) during the lead-in period to 1.51 (95% CI, 0.81 to 2.82) during months 7 through 18 after treatment, for a rate ratio of 0.36 (95% Wald CI, 0.20 to 0.64; P<0.001), demonstrating noninferiority and superiority of etranacogene dezaparvovec as compared with factor IX prophylaxis. Factor IX activity had increased from baseline by a least-squares mean of 36.2 percentage points (95% CI, 31.4 to 41.0) at 6 months and 34.3 percentage points (95% CI, 29.5 to 39.1) at 18 months after treatment, and usage of factor IX concentrate decreased by a mean of 248,825 IU per year per participant in the post-treatment period (P<0.001 for all three comparisons). Benefits and safety were observed in participants with predose AAV5 neutralizing antibody titers of less than 700. No treatment-related serious adverse events occurred. Conclusions: Etranacogene dezaparvovec gene therapy was superior to prophylactic factor IX with respect to the annualized bleeding rate, and it had a favorable safety profile.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Leebeek, Frank W.G.Erasmus University Medical Center
(author)
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Recht, MichaelYale University
(author)
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Key, Nigel S.University of North Carolina
(author)
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Castaman, GiancarloCareggi University Hospital
(author)
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Miesbach, WolfgangUniversity Hospital Frankfurt
(author)
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Lattimore, SusanYale University
(author)
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Peerlinck, KathelijneUniversity Hospitals Leuven
(author)
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Van Der Valk, PaulUniversity Medical Center Utrecht
(author)
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Coppens, MichielAcademic Medical Center of University of Amsterdam (AMC)
(author)
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Kampmann, PeterCopenhagen University Hospital
(author)
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Meijer, KarinaUniversity Medical Center Groningen
(author)
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O'connell, Niamh
(author)
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Pasi, K. JohnQueen Mary University
(author)
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Hart, Daniel P.Royal London Hospital,Queen Mary University
(author)
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Kazmi, RashidUniversity Hospital Southampton
(author)
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Astermark, JanLund University,Lunds universitet,Klinisk koagulationsmedicin, Malmö,Forskargrupper vid Lunds universitet,Clinical Coagulation, Malmö,Lund University Research Groups,Skåne University Hospital(Swepub:lu)medf-jas
(author)
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Hermans, Cedric R.J.R.Catholic University of Louvain,Saint-Luc University Hospital
(author)
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Klamroth, RobertUniversity Hospital Bonn,Vivantes hospital im Friedrichshain
(author)
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Lemons, RichardUniversity of Utah
(author)
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Visweshwar, NathanUniversity of South Florida
(author)
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Von Drygalski, Annette
(author)
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Young, GuyUniversity of Southern California
(author)
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Crary, Shelley E.University of Arkansas for Medical Sciences
(author)
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Escobar, MiguelUniversity of Texas Health Science Center at Houston
(author)
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Gomez, Esteban
(author)
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Kruse-Jarres, RebeccaUniversity of Washington
(author)
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Quon, Doris V.
(author)
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Symington, EmilyAddenbrooke's Hospital
(author)
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Wang, MichaelUniversity of Colorado
(author)
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Wheeler, Allison P.Vanderbilt University Medical Center
(author)
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Gut, Robert
(author)
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Liu, Ying P.UniQure Biopharma
(author)
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Dolmetsch, Ricardo E.
(author)
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Cooper, David L.
(author)
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Li, Yanyan
(author)
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Goldstein, Brahm
(author)
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Monahan, Paul E.
(author)
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University of MichiganErasmus University Medical Center
(creator_code:org_t)
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In:New England Journal of Medicine388:8, s. 706-7180028-4793
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Pipe, Steven W.
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Leebeek, Frank W ...
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Recht, Michael
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Key, Nigel S.
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Castaman, Gianca ...
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Miesbach, Wolfga ...
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Lattimore, Susan
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Peerlinck, Kathe ...
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Van Der Valk, Pa ...
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Coppens, Michiel
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Kampmann, Peter
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Meijer, Karina
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O'connell, Niamh
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Pasi, K. John
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Hart, Daniel P.
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Kazmi, Rashid
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Astermark, Jan
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Hermans, Cedric ...
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Klamroth, Robert
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Lemons, Richard
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Visweshwar, Nath ...
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Von Drygalski, A ...
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Young, Guy
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Crary, Shelley E ...
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Escobar, Miguel
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Gomez, Esteban
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Kruse-Jarres, Re ...
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Quon, Doris V.
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Symington, Emily
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Wang, Michael
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Wheeler, Allison ...
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Gut, Robert
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Liu, Ying P.
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Dolmetsch, Ricar ...
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Cooper, David L.
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Li, Yanyan
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Goldstein, Brahm
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Monahan, Paul E.
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