PMID- 36490302 OWN - NLM STAT- MEDLINE DCOM- 20231031 LR - 20231031 IS - 2473-9537 (Electronic) IS - 2473-9529 (Print) IS - 2473-9529 (Linking) VI - 7 IP - 19 DP - 2023 Oct 10 TI - Stable and durable factor IX levels in patients with hemophilia B over 3 years after etranacogene dezaparvovec gene therapy. PG - 5671-5679 LID - 10.1182/bloodadvances.2022008886 [doi] AB - Etranacogene dezaparvovec (AMT-061) is a recombinant adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX (FIX) transgene with a liver-specific promoter. Here, we report 3-year outcomes from a phase 2b, open-label, single-dose, single-arm, multicenter trial conducted among adults with severe or moderately severe hemophilia B (FIX /=5% at 6 weeks was met. Secondary end points included bleed frequency, FIX concentrate use, joint health, and adverse events (AEs). All participants required routine FIX prophylaxis and had neutralizing antibodies to AAV5 before etranacogene dezaparvovec treatment. After administration, FIX activity rose to a mean of 40.8% in year 1 and was sustained in year 3 at 36.9%. All participants discontinued FIX prophylaxis. Bleeding was completely eliminated in 2 out of 3 participants. One participant required on-demand FIX replacement therapy per protocol because of elective surgical procedures, for 2 reported bleeding episodes, and twice for a single self-administered infusion because of an unreported reason. One participant experienced 2 mild, self-limiting AEs shortly after dosing. During the 3-year study period, there were no clinically significant elevations in liver enzymes, no requirement for steroids, no FIX inhibitor development, and no late-emergent safety events in any participant. Etranacogene dezaparvovec was safe and effective in adults with hemophilia B over 3 years after administration. This trial was registered at www.clinicaltrials.gov as #NCT03489291. CI - (c) 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. FAU - von Drygalski, Annette AU - von Drygalski A AD - Division of Hematology/Oncology, Department of Medicine, University of California San Diego, San Diego, CA. FAU - Gomez, Esteban AU - Gomez E AD - Center for Inherited Blood Disorders, Orange, CA. FAU - Giermasz, Adam AU - Giermasz A AD - Division of Hematology/Oncology, Department of Medicine, Hemophilia Treatment Center, University of California Davis, Sacramento, CA. FAU - Castaman, Giancarlo AU - Castaman G AD - Center for Bleeding Disorders, Department of Oncology, Careggi University Hospital, Florence, Italy. FAU - Key, Nigel S AU - Key NS AD - Division of Hematology and Blood Research Center, Department of Medicine, University of North Carolina, Chapel Hill, NC. FAU - Lattimore, Susan U AU - Lattimore SU AD - The Hemophilia Center, Oregon Health & Science University, Portland, OR. FAU - Leebeek, Frank W G AU - Leebeek FWG AD - Department of Hematology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. FAU - Miesbach, Wolfgang A AU - Miesbach WA AD - Department of Hemostaseology and Hemophilia Center, Medical Clinic 2, Institute of Transfusion Medicine, University Hospital Frankfurt, Frankfurt, Germany. FAU - Recht, Michael AU - Recht M AUID- ORCID: 0000-0002-2805-1016 AD - American Thrombosis and Hemostasis Network, Rochester, NY. AD - Hemophilia Treatment Center, Yale University School of Medicine, New Haven, CT. FAU - Gut, Robert AU - Gut R AD - uniQure Inc, Lexington, MA. FAU - Dolmetsch, Ricardo AU - Dolmetsch R AD - uniQure Inc, Lexington, MA. FAU - Monahan, Paul E AU - Monahan PE AD - CSL Behring, King of Prussia, PA. FAU - Le Quellec, Sandra AU - Le Quellec S AUID- ORCID: 0000-0002-6203-3946 AD - CSL Behring Europe, Hattersheim am Main, Germany. FAU - Pipe, Steven W AU - Pipe SW AD - Departments of Pediatrics and Pathology, University of Michigan, Ann Arbor, MI. LA - eng SI - ClinicalTrials.gov/NCT03489291 PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't PL - United States TA - Blood Adv JT - Blood advances JID - 101698425 RN - 9001-28-9 (Factor IX) RN - Adeno-associated virus-5 SB - IM MH - Adult MH - Humans MH - Dependovirus/genetics MH - Factor IX/genetics MH - Genetic Therapy/methods MH - *Hemophilia B/drug therapy/genetics MH - Hemorrhage/etiology PMC - PMC10539871 COIS- Conflict-of-interest disclosure: A.v.D. is a consultant for BioMarin, Sanofi Genzyme, Novo Nordisk, Pfizer, uniQure, and Hematherix. A.G. is a consultant for Bioverativ, Genentech/Roche, BioMarin, and uniQure and serves as a speaker bureau of Bioverativ and Genentech/Roche. G.C. received grants/research support from CSL Behring, Pfizer, and Sobi and serves as a speaker bureau of Bayer, BioMarin, Roche, Sobi, Grifols, LFB, Novo Nordisk, Werfen, Kedrion, and uniQure. N.S.K. received grants/research support from Grifols and Takeda and is a consultant for uniQure, BioMarin, and Novo Nordisk. S.U.L is a consultant for uniQure. F.W.G.L. received grants/research support from CSL Behring, Shire/Takeda, Roche, and Sobi and is a consultant for uniQure, Takeda, Novo Nordisk, and BioMarin. W.A.M. received grants/research support from Bayer, Biotest, Takeda, LFB, Octapharma, Novo Nordisk, Pfizer, and uniQure and is a consultant for Bayer, BioMarin, Freeline, LFB, Octapharma, Novo Nordisk, Pfizer, and uniQure. M.R. received research funding from Bayer, BioMarin, CSL Behring, Genentech, Grifols, Hema Biologics, LFB, Novo Nordisk, Octapharma, Pfizer, Sanofi, Spark Therapeutics, Takeda, and uniQure; is a consultant for Catalyst Biosciences, CSL Behring, Genentech, Hema Biologics, Kedrion, Novo Nordisk, Pfizer, Sanofi, Takeda, and uniQure; and is on the board of directors for Foundation for Women and Girls with Blood Disorders, Partners in Bleeding Disorders Education, and Thrombosis and Hemostasis Societies of North America. E.G. serves as a speaker bureau of Global Blood Therapeutics. R.G. is an employee of uniQure. R.D. is an employee of uniQure. S.L.Q. is an employee of CSL Behring. P.E.M. is an employee of CSL Behring. S.W.P. received a grant/research support from Bayer, BioMarin, Freeline, Novo Nordisk, and Roche/Genentech and is a consultant for ApcinteX, ASC Therapeutics, Bayer, BioMarin, CSL Behring, GeneVentiv, HEMA Biologics, Freeline Therapeutics, Novo Nordisk, Pfizer, Regeneron/Intellia, Roche/Genentech, Sanofi, Spark Therapeutics, Takeda, and uniQure. EDAT- 2022/12/10 06:00 MHDA- 2023/10/23 12:42 PMCR- 2022/12/11 CRDT- 2022/12/09 13:44 PHST- 2022/11/25 00:00 [accepted] PHST- 2022/09/12 00:00 [received] PHST- 2023/10/23 12:42 [medline] PHST- 2022/12/10 06:00 [pubmed] PHST- 2022/12/09 13:44 [entrez] PHST- 2022/12/11 00:00 [pmc-release] AID - 493567 [pii] AID - 10.1182/bloodadvances.2022008886 [doi] PST - ppublish SO - Blood Adv. 2023 Oct 10;7(19):5671-5679. doi: 10.1182/bloodadvances.2022008886.