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Gene Therapy with E...
Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B
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- Pipe, Steven W. (författare)
- University of Michigan
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- Leebeek, Frank W.G. (författare)
- Erasmus University Medical Center
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- Recht, Michael (författare)
- Yale University
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- Key, Nigel S. (författare)
- University of North Carolina
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- Castaman, Giancarlo (författare)
- Careggi University Hospital
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- Miesbach, Wolfgang (författare)
- University Hospital Frankfurt
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- Lattimore, Susan (författare)
- Yale University
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- Peerlinck, Kathelijne (författare)
- University Hospitals Leuven
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- Van Der Valk, Paul (författare)
- University Medical Center Utrecht
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- Coppens, Michiel (författare)
- Academic Medical Center of University of Amsterdam (AMC)
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- Kampmann, Peter (författare)
- Copenhagen University Hospital
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- Meijer, Karina (författare)
- University Medical Center Groningen
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O'connell, Niamh (författare)
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- Pasi, K. John (författare)
- Queen Mary University
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- Hart, Daniel P. (författare)
- Royal London Hospital,Queen Mary University
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- Kazmi, Rashid (författare)
- University Hospital Southampton
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- Astermark, Jan (författare)
- Lund University,Lunds universitet,Klinisk koagulationsmedicin, Malmö,Forskargrupper vid Lunds universitet,Clinical Coagulation, Malmö,Lund University Research Groups,Skåne University Hospital
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- Hermans, Cedric R.J.R. (författare)
- Catholic University of Louvain,Saint-Luc University Hospital
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- Klamroth, Robert (författare)
- University Hospital Bonn,Vivantes hospital im Friedrichshain
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- Lemons, Richard (författare)
- University of Utah
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- Visweshwar, Nathan (författare)
- University of South Florida
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Von Drygalski, Annette (författare)
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- Young, Guy (författare)
- University of Southern California
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- Crary, Shelley E. (författare)
- University of Arkansas for Medical Sciences
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- Escobar, Miguel (författare)
- University of Texas Health Science Center at Houston
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Gomez, Esteban (författare)
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- Kruse-Jarres, Rebecca (författare)
- University of Washington
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Quon, Doris V. (författare)
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- Symington, Emily (författare)
- Addenbrooke's Hospital
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- Wang, Michael (författare)
- University of Colorado
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- Wheeler, Allison P. (författare)
- Vanderbilt University Medical Center
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Gut, Robert (författare)
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- Liu, Ying P. (författare)
- UniQure Biopharma
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Dolmetsch, Ricardo E. (författare)
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Cooper, David L. (författare)
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Li, Yanyan (författare)
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Goldstein, Brahm (författare)
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Monahan, Paul E. (författare)
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(creator_code:org_t)
- 2023
- 2023
- Engelska 13 s.
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 388:8, s. 706-718
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Nyckelord
- Childhood Diseases
- Coagulation
- Genetics
- Genetics General
- Hematology/Oncology
- Pediatrics
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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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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visa fler...
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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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visa färre...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Hematologi
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New England Jour ...
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