
Gene therapy for hemophilia: Recent developments and challenges (Review)
- Authors:
- Marwa Ali Abdulnabi
- Enass Abdul Kareem Dagher Al‑Saadi
- Israa M. Al‑Bayaa
-
Affiliations: Department of Pathology, Al-Kindy College of Medicine, University of Baghdad, Baghdad 10045, Iraq, Department of Pathology, College of Medicine, University of Kerbala, Kerbala 56001, Iraq - Published online on: February 28, 2025 https://doi.org/10.3892/wasj.2025.329
- Article Number: 41
-
Copyright : © Ali Abdulnabi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
This article is mentioned in:
Abstract
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Bolton-Maggs PH and Pasi KJ: Haemophilias A and B. Lancet. 361:1801–1809. 2003.PubMed/NCBI View Article : Google Scholar | |
Iorio A, Stonebraker JS, Chambost H, Makris M, Coffin D, Herr C and Germini F: Data and Demographics Committee of the World Federation of Hemophilia. Establishing the prevalence and prevalence at birth of hemophilia in males: A meta-analytic approach using national registries. Ann Intern Med. 171:540–546. 2019.PubMed/NCBI View Article : Google Scholar | |
Kavaklı K, Antmen B, Okan V, Şahin F, Aytaç S, Balkan C, Berber E, Kaya Z, Küpesiz A and Zülfikar B: Gene therapy in haemophilia: Literature review and regional perspectives for Turkey. Ther Adv Hematol. 13(20406207221104591)2022.PubMed/NCBI View Article : Google Scholar | |
Bolous NS, Bhatt N, Bhakta N, Neufeld EJ, Davidoff AM and Reiss UM: Gene therapy and hemophilia: Where do we go from here? J Blood Med. 13:559–580. 2022.PubMed/NCBI View Article : Google Scholar | |
World Federation of Hemophilia: The report on the WFH annual global survey 2020: World Federation of Hemophilia, 2021. Available from: https://www1.wfh.org/publications/files/pdf-2045.pdf. | |
Kadhim KAR, Al-Lami FH and Baldawi KH: Epidemiological profile of hemophilia in Baghdad-Iraq. Inquiry. 56(46958019845280)2019.PubMed/NCBI View Article : Google Scholar | |
Abdulsalam AH, Al-Rahal NK and Ghiath Y: Inherited bleeding disorders in pediatric patients; experience of the national referral center in Iraq. Indian J Hematol Blood Transfus. 37:96–100. 2021.PubMed/NCBI View Article : Google Scholar | |
Hassan S, Monahan RC, Mauser-Bunschoten EP, van Vulpen LFD, Eikenboom J, Beckers EAM, Hooimeijer L, Ypma PF, Nieuwenhuizen L, Coppens M, et al: Mortality, life expectancy, and causes of death of persons with hemophilia in the Netherlands 2001-2018. J Thromb Haemost. 19:645–653. 2021.PubMed/NCBI View Article : Google Scholar | |
Coffin D, Gouider E, Konkle B, Hermans C, Lambert C, Diop S, Ayoub E, Tootoonchian E, Youttananukorn T, Dakik P, et al: The world federation of hemophilia world bleeding disorders registry: Insights from the first 10,000 patients. Res Pract Thromb Haemost. 7(102264)2023.PubMed/NCBI View Article : Google Scholar | |
Taresh AK and Hassan MK: Inhibitors among patients with hemophilia in Basra, Iraq-A single center experience. Niger J Clin Pract. 22:416–421. 2019.PubMed/NCBI View Article : Google Scholar | |
Lateef IA: Evaluation of the clinical status of patients with inherited bleeding disorders in Diyala-Iraq. Diyala J Medicine. 9:23–29. 2015. | |
Lateef IA, Hamood HJ and Khaleel OA: Spectrum of hemophilia in Diyala-Iraq. Diyala J Medicine. 10:53–58. 2016. | |
Sharma A, Mathew ME, Sriganesh V and Reiss UM: Gene therapy for haemophilia. Cochrane Database Syst Rev. 4(CD010822)2020.PubMed/NCBI View Article : Google Scholar | |
Srivastava A, Santagostino E, Dougall A, Kitchen S, Sutherland M, Pipe SW, Carcao M, Mahlangu J, Ragni MV, Windyga J, et al: WFH guidelines for the management of hemophilia. Haemophilia. 26:1–158. 2020.PubMed/NCBI View Article : Google Scholar | |
Nathwani AC: Gene therapy for hemophilia. Hematology Am Soc Hematol Educ Program. 2019:1–8. 2019.PubMed/NCBI View Article : Google Scholar | |
Wang X, Shin SC, Chiang AF, Khan I, Pan D, Rawlings DJ and Miao CH: Intraosseous delivery of lentiviral vectors targeting factor VIII expression in platelets corrects murine hemophilia A. Mol Ther. 23:617–626. 2015.PubMed/NCBI View Article : Google Scholar | |
Doncel SS, Mosquera GA, Pelaez RG, Cortes JM, Rico CA, Cadavid FJ, Plazas NR, Amar IAP, Siado JEP, Rey FAP, et al: Genetic characterization of the factor VIII gene in a cohort of colombian patients with severe hemophilia A with inhibitors. Hematol Rep. 14:149–154. 2022.PubMed/NCBI View Article : Google Scholar | |
Hassan MM and Jabber AD: Identification of factor VIII gene mutations in Iraqi patient with hemophilia A. Int J Med Res Prof. 2:192–199. 2016. | |
Abdulqader AMR, Mohammed AI, Rachid S, Ghoraishizadeh P and Mahmood SN: Identification of the intron 22 and intron 1 inversions of the factor VIII gene in Iraqi Kurdish patients with hemophilia A. Clin Appl Thromb Hemost. 26(1076029619888293)2020.PubMed/NCBI View Article : Google Scholar | |
Lisowski L, Staber JM, Wright JF and Valentino LA: The intersection of vector biology, gene therapy, and hemophilia. Res Pract Thromb Haemost. 5(e12586)2021.PubMed/NCBI View Article : Google Scholar | |
Palmer TD, Thompson AR and Miller AD: Production of human factor IX in animals by genetically modified skin fibroblasts: Potential therapy for hemophilia B. Blood. 73:438–445. 1989.PubMed/NCBI | |
Nathwani AC, Tuddenham EG, Rangarajan S, Rosales C, McIntosh J, Linch DC, Chowdary P, Riddell A, Pie AJ, Harrington C, et al: Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N Engl J Med. 365:2357–2365. 2011.PubMed/NCBI View Article : Google Scholar | |
Niemeyer GP, Herzog RW, Mount J, Arruda VR, Tillson DM, Hathcock J, van Ginkel FW, High KA and Lothrop CD Jr: Long-term correction of inhibitor-prone hemophilia B dogs treated with liver-directed AAV2-mediated factor IX gene therapy. Blood. 113:797–806. 2009.PubMed/NCBI View Article : Google Scholar | |
Liao G, Nayak S, Regueiro JR, Berger SB, Detre C, Romero X, de Waal Malefyt R, Chatila TA, Herzog RW and Terhorst C: GITR engagement preferentially enhances proliferation of functionally competent CD4+ CD25+ FoxP3+ regulatory T cells. Int Immunol. 22:259–270. 2010.PubMed/NCBI View Article : Google Scholar | |
Cooper M, Nayak S, Hoffman BE, Terhorst C, Cao O and Herzog RW: Improved induction of immune tolerance to factor IX by hepatic AAV-8 gene transfer. Hum Gene Ther. 20:767–776. 2009.PubMed/NCBI View Article : Google Scholar | |
Mátrai J, Chuah MKL and VandenDriessche T: Preclinical and clinical progress in hemophilia gene therapy. Curr Opin Hematol. 17:387–392. 2010.PubMed/NCBI View Article : Google Scholar | |
Rangarajan S, Walsh L, Lester W, Perry D, Madan B, Laffan M, Yu H, Vettermann C, Pierce GF, Wong WY and Pasi KJ: AAV5-factor VIII gene transfer in severe hemophilia A. N Engl J Med. 377:2519–2530. 2017.PubMed/NCBI View Article : Google Scholar | |
Guo XL, Chung TH, Qin Y, Zheng J, Zheng H, Sheng L, Wynn T and Chang LJ: Hemophilia gene therapy: New development from bench to bed side. Curr Gene Ther. 19:264–273. 2019.PubMed/NCBI View Article : Google Scholar | |
Xu L, Nichols TC, Sarkar R, McCorquodale S, Bellinger DA and Ponder KP: Absence of a desmopressin response after therapeutic expression of factor VIII in hemophilia A dogs with liver-directed neonatal gene therapy. Proc Natl Acad Sci USA. 102:6080–6085. 2005.PubMed/NCBI View Article : Google Scholar | |
Milani M, Canepari C, Liu T, Biffi M, Russo F, Plati T, Curto R, Patarroyo-White S, Drager D, Visigalli I, et al: Liver-directed lentiviral gene therapy corrects hemophilia A mice and achieves normal-range factor VIII activity in non-human primates. Nat Commun. 13(2454)2022.PubMed/NCBI View Article : Google Scholar | |
Tsui LV, Kelly M, Zayek N, Rojas V, Ho K, Ge Y, Moskalenko M, Mondesire J, Davis J, Roey MV, et al: Production of human clotting Factor IX without toxicity in mice after vascular delivery of a lentiviral vector. Nat Biotechnol. 20:53–57. 2002.PubMed/NCBI View Article : Google Scholar | |
Stein CS, Kang Y, Sauter SL, Townsend K, Staber P, Derksen TA, Martins I, Qian J, Davidson BL and McCray PB Jr: In vivo treatment of hemophilia A and mucopolysaccharidosis type VII using nonprimate lentiviral vectors. Mol Ther. 3:850–856. 2001.PubMed/NCBI View Article : Google Scholar | |
Dull T, Zufferey R, Kelly M, Mandel RJ, Nguyen M, Trono D and Naldini L: A third-generation lentivirus vector with a conditional packaging system. J Virol. 72:8463–8471. 1998.PubMed/NCBI View Article : Google Scholar | |
Kuether EL, Schroeder JA, Fahs SA, Cooley BC, Chen Y, Montgomery RR, Wilcox DA and Shi Q: Lentivirus-mediated platelet gene therapy of murine hemophilia A with pre-existing anti-factor VIII immunity. J Thromb Haemost. 10:1570–1580. 2012.PubMed/NCBI View Article : Google Scholar | |
Roth DA, Tawa NE Jr, O'Brien JM, Treco DA and Selden RF: Factor VIII Transkaryotic Therapy Study Group. Nonviral transfer of the gene encoding coagulation factor VIII in patients with severe hemophilia A. N Engl J Med. 344:1735–1742. 2001.PubMed/NCBI View Article : Google Scholar | |
Spira J, Plyushch OP, Andreeva TA and Andreev Y: Prolonged bleeding-free period following prophylactic infusion of recombinant factor VIII reconstituted with pegylated liposomes. Blood. 108:3668–3673. 2006.PubMed/NCBI View Article : Google Scholar | |
Di Minno G, Cerbone AM, Coppola A, Cimino E, Di Capua M, Pamparana F, Tufano A and Di Minno MN: Longer-acting factor VIII to overcome limitations in haemophilia management: The PEGylated liposomes formulation issue. Haemophilia. 16:2–6. 2010.PubMed/NCBI View Article : Google Scholar | |
Lu DR, Zhou JM, Zheng B, Qiu XF, Xue JL, Wang JM, Meng PL, Han FL, Ming BH and Wang XP: Stage I clinical trial of gene therapy for hemophilia B. Sci China B. 36:1342–1351. 1993.PubMed/NCBI | |
Manno CS, Pierce GF, Arruda VR, Glader B, Ragni M, Rasko JJ, Ozelo MC, Hoots K, Blatt P, Konkle B, et al: Successful transduction of liver in hemophilia by AAV-factor IX and limitations imposed by the host immune response. Nat Med. 12:342–347. 2006.PubMed/NCBI View Article : Google Scholar | |
Crudele JM, Finn JD, Siner JI, Martin NB, Niemeyer GP, Zhou S, Mingozzi F, Lothrop CD Jr and Arruda VR: AAV liver expression of FIX-Padua prevents and eradicates FIX inhibitor without increasing thrombogenicity in hemophilia B dogs and mice. Blood. 125:1553–1561. 2015.PubMed/NCBI View Article : Google Scholar | |
Von Drygalski A, Giermasz A, Castaman G, Key NS, Lattimore S, Leebeek FWG, Miesbach W, Recht M, Long A, Gut R, et al: Etranacogene dezaparvovec (AMT-061 phase 2b): Normal/near normal FIX activity and bleed cessation in hemophilia B. Blood Adv. 3:3241–3247. 2019.PubMed/NCBI View Article : Google Scholar | |
Pipe SW, Leebeek FWG, Recht M, Key NS, Castaman G, Miesbach W, Lattimore S, Peerlinck K, Van der Valk P, Coppens M, et al: Gene therapy with etranacogene dezaparvovec for hemophilia B. N Engl J Med. 388:706–718. 2023.PubMed/NCBI View Article : Google Scholar | |
Pipe SW, Reddy KR and Chowdary P: Gene therapy: Practical aspects of implementation. Haemophilia. 28 (Suppl 4):S44–S52. 2022.PubMed/NCBI View Article : Google Scholar | |
Pasi KJ, Laffan M, Rangarajan S, Robinson TM, Mitchell N, Lester W, Symington E, Madan B, Yang X, Kim B, et al: Persistence of haemostatic response following gene therapy with valoctocogene roxaparvovec in severe haemophilia A. Haemophilia. 27:947–956. 2021.PubMed/NCBI View Article : Google Scholar | |
Pasi KJ, Rangarajan S, Mitchell N, Lester W, Symington E, Madan B, Laffan M, Russell CB, Li M, Pierce GF and Wong WY: Multiyear follow-up of AAV5-hFVIII-SQ gene therapy for hemophilia A. N Engl J Med. 382:29–40. 2020.PubMed/NCBI View Article : Google Scholar | |
Ozelo MC, Mahlangu J, Pasi KJ, Giermasz A, Leavitt AD, Laffan M, Symington E, Quon DV, Wang JD, Peerlinck K, et al: Valoctocogene roxaparvovec gene therapy for hemophilia A. N Engl J Med. 386:1013–1025. 2022.PubMed/NCBI View Article : Google Scholar | |
Long BR, Veron P, Kuranda K, Hardet R, Mitchell N, Hayes GM, Wong WY, Lau K, Li M, Hock MB, et al: Early phase clinical immunogenicity of valoctocogene roxaparvovec, an AAV5-mediated gene therapy for hemophilia A. Mol Ther. 29:597–610. 2021.PubMed/NCBI View Article : Google Scholar | |
Visweshwar N, Harrington TJ, Leavitt AD, Konkle BA, Giermasz A, Stine K, 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. 138 (Suppl 1)(564)2021. | |
Elkouby L, Armour SM, Toso R, DiPietro M, Davidson RJ, Nguyen GN, Willet M, Kutza S, Silverberg J, Frick J, et al: Preclinical assessment of an optimized AAV-FVIII vector in mice and non-human primates for the treatment of hemophilia A. Mol Ther Methods Clin Dev. 24:20–29. 2022.PubMed/NCBI View Article : Google Scholar | |
George LA, Monahan PE, Eyster ME, Sullivan SK, Ragni MV, Croteau SE, Rasko JEJ, Recht M, Samelson-Jones BJ, MacDougall A, et al: Multiyear factor VIII expression after AAV gene transfer for hemophilia A. N Engl J Med. 385:1961–1973. 2021.PubMed/NCBI View Article : Google Scholar | |
Barbon E, Ayme G, Mohamadi A, Ottavi JF, Kawecki C, Casari C, Verhenne S, Marmier S, van Wittenberghe L, Charles S, et al: Single-domain antibodies targeting antithrombin reduce bleeding in hemophilic mice with or without inhibitors. EMBO Mol Med. 12(e11298)2020.PubMed/NCBI View Article : Google Scholar | |
Setten RL, Rossi JJ and Han SP: The current state and future directions of RNAi-based therapeutics. Nat Rev Drug Discov. 18:421–446. 2019.PubMed/NCBI View Article : Google Scholar | |
Patnaik MM and Moll S: Inherited antithrombin deficiency: A review. Haemophilia. 14:1229–1239. 2008.PubMed/NCBI View Article : Google Scholar | |
Pasi KJ, Rangarajan S, Georgiev P, Mant T, Creagh MD, Lissitchkov T, Bevan D, Austin S, Hay CR, Hegemann I, et al: Targeting of antithrombin in hemophilia A or B with RNAi therapy. N Engl J Med. 377:819–828. 2017.PubMed/NCBI View Article : Google Scholar | |
Dargaud Y, Béguin S, Lienhart A, Al Dieri R, Trzeciak C, Bordet JC, Hemker HC and Negrier C: Evaluation of thrombin generating capacity in plasma from patients with haemophilia A and B. Thromb Haemost. 93:475–480. 2005.PubMed/NCBI View Article : Google Scholar | |
Segurado OG, Jiang R and Pipe SW: Challenges and opportunities when transitioning from in vivo gene replacement to in vivo CRISPR/Cas9 therapies-a spotlight on hemophilia. Expert Opin Biol Ther. 22:1091–1098. 2022.PubMed/NCBI View Article : Google Scholar | |
Chen H, Shi M, Gilam A, Zheng Q, Zhang Y, Afrikanova I, Li J, Gluzman Z, Jiang R, Kong LJ, et al: Hemophilia A ameliorated in mice by CRISPR-based in vivo genome editing of human factor VIII. Sci Rep. 9(16838)2019.PubMed/NCBI View Article : Google Scholar | |
Anguela XM, Sharma R, Doyon Y, Miller JC, Li H, Haurigot V, Rohde ME, Wong SY, Davidson RJ, Zhou S, et al: Robust ZFN-mediated genome editing in adult hemophilic mice. Blood. 122:3283–3287. 2013.PubMed/NCBI View Article : Google Scholar | |
Shi Q: Platelet-targeted gene therapy for hemophilia. Mol Ther Methods Clin Dev. 9:100–108. 2018.PubMed/NCBI View Article : Google Scholar | |
Nayak S and Herzog RW: Progress and prospects: Immune responses to viral vectors. Gene Ther. 17:295–304. 2010.PubMed/NCBI View Article : Google Scholar | |
Salas D, Kwikkers KL, Zabaleta N, Bazo A, Petry H, van Deventer SJ, Aseguinolaza GG and Ferreira V: Immunoadsorption enables successful rAAV5-mediated repeated hepatic gene delivery in nonhuman primates. Blood Adv. 3:2632–2641. 2019.PubMed/NCBI View Article : Google Scholar | |
Ferla R, Claudiani P, Savarese M, Kozarsky K, Parini R, Scarpa M, Donati MA, Sorge G, Hopwood JJ, Parenti G, et al: Prevalence of anti-adeno-associated virus serotype 8 neutralizing antibodies and arylsulfatase B cross-reactive immunologic material in mucopolysaccharidosis VI patient candidates for a gene therapy trial. Hum Gene Ther. 26:145–152. 2015.PubMed/NCBI View Article : Google Scholar | |
Elmore ZC, Oh DK, Simon KE, Fanous MM and Asokan A: Rescuing AAV gene transfer from neutralizing antibodies with an IgG-degrading enzyme. JCI Insight. 5(e139881)2020.PubMed/NCBI View Article : Google Scholar | |
Follenzi A, Santambrogio L and Annoni A: Immune responses to lentiviral vectors. Curr Gene Ther. 7:306–315. 2007.PubMed/NCBI View Article : Google Scholar | |
Limberis MP, Bell CL, Heath J and Wilson JM: Activation of transgene-specific T cells following lentivirus-mediated gene delivery to mouse lung. Mol Ther. 18:143–150. 2010.PubMed/NCBI View Article : Google Scholar | |
Geisler A and Fechner H: MicroRNA-regulated viral vectors for gene therapy. World J Exp Med. 6:37–54. 2016.PubMed/NCBI View Article : Google Scholar | |
Chen Y, Schroeder JA, Gao C, Li J, Hu J and Shi Q: In vivo enrichment of genetically manipulated platelets for murine hemophilia B gene therapy. J Cell Physiol. 236:354–365. 2021.PubMed/NCBI View Article : Google Scholar | |
Lundstrom K: Viral vectors in gene therapy: Where do we stand in 2023? Viruses. 15(698)2023.PubMed/NCBI View Article : Google Scholar | |
Nathwani AC, Rosales C, McIntosh J, Rastegarlari G, Nathwani D, Raj D, Nawathe S, Waddington SN, Bronson R, Jackson S, et al: Long-term safety and efficacy following systemic administration of a self-complementary AAV vector encoding human FIX pseudotyped with serotype 5 and 8 capsid proteins. Mol Ther. 19:876–885. 2011.PubMed/NCBI View Article : Google Scholar | |
Nathwani AC, Reiss UM, Tuddenham EG, Rosales C, Chowdary P, McIntosh J, Peruta MD, Lheriteau E, Patel N, Raj D, et al: Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med. 371:1994–2004. 2014.PubMed/NCBI View Article : Google Scholar | |
Batty P and Lillicrap D: Hemophilia gene therapy: Approaching the first licensed product. Hemasphere. 5(e540)2021.PubMed/NCBI View Article : Google Scholar | |
Chandler RJ, LaFave MC, Varshney GK, Trivedi NS, Carrillo-Carrasco N, Senac JS, Wu W, Hoffmann V, Elkahloun AG, Burgess SM and Venditti CP: Vector design influences hepatic genotoxicity after adeno-associated virus gene therapy. J Clin Invest. 125:870–880. 2015.PubMed/NCBI View Article : Google Scholar | |
Fong S, Rangarajan S and Mitchell N: First in human liver biopsy study following gene therapy for hemophilia A. Res Pract Thromb Haemost. 4(3)2020. | |
Marcucci KT, Jadlowsky JK, Hwang WT, Suhoski-Davis M, Gonzalez VE, Kulikovskaya I, Gupta M, Lacey SF, Plesa G, Chew A, et al: Retroviral and lentiviral safety analysis of gene-modified T cell products and infused HIV and oncology patients. Mol Ther. 26:269–279. 2018.PubMed/NCBI View Article : Google Scholar | |
Arruda VR, Fields PA, Milner R, Wainwright L, De Miguel MP, Donovan PJ, Herzog RW, Nichols TC, Biegel JA, Razavi M, et al: Lack of germline transmission of vector sequences following systemic administration of recombinant AAV-2 vector in males. Mol Ther. 4:586–592. 2001.PubMed/NCBI View Article : Google Scholar | |
Favaro P, Downey HD, Zhou JS, Wright JF, Hauck B, Mingozzi F, High KA and Arruda VR: Host and vector-dependent effects on the risk of germline transmission of AAV vectors. Mol Ther. 17:1022–1030. 2009.PubMed/NCBI View Article : Google Scholar | |
Food and Drug Administration: Guidance for industry: Gene therapy clinical trials-Observing subjects for delayed adverse events. 2006. | |
Leebeek FWG, Meijer K, Coppens M, Kampmann P, Klamroth R, Schutgens R, Castaman G, Seifried E, Schwaeble J, Bönig H, et al: AMT-060 gene therapy in adults with severe or moderate-severe hemophilia B confirm stable FIX expression and durable reductions in bleeding and factor IX consumption for up to 5 years. Blood. 136(26)2020. | |
Sabatino DE, Lange AM, Altynova ES, Sarkar R, Zhou S, Merricks EP, Franck HG, Nichols TC, Arruda VR and Kazazian HH Jr: Efficacy and safety of long-term prophylaxis in severe hemophilia A dogs following liver gene therapy using AAV vectors. Mol Ther. 19:442–449. 2011.PubMed/NCBI View Article : Google Scholar | |
Gollomp KL, Doshi BS and Arruda VR: Gene therapy for hemophilia: Progress to date and challenges moving forward. Transfus Apher Sci. 58:602–612. 2019.PubMed/NCBI View Article : Google Scholar | |
Samori Z and Badran I: Somatic gene therapy: Ethical consideration and Islamic Fiqhi perspective. J Engineering and Applied Sciences. 13:4353–4561. 2018. | |
Bolous NS, Chen Y, Wang H, Davidoff AM, Devidas M, Jacobs TW, Meagher MM, Nathwani AC, Neufeld EJ, Piras BA, et al: The cost-effectiveness of gene therapy for severe hemophilia B: A microsimulation study from the United States perspective. Blood. 138:1677–1690. 2021.PubMed/NCBI View Article : Google Scholar | |
Reiss UM, Zhang L and Ohmori T: Hemophilia gene therapy-New country initiatives. Haemophilia. 27:132–141. 2021.PubMed/NCBI View Article : Google Scholar | |
Goodman C, Berntorp E and Wong O: International Haemophilia Access Strategy Council. Alternative payment models for durable and potentially curative therapies: The case of gene therapy for haemophilia A. Haemophilia. 28:27–34. 2022.PubMed/NCBI View Article : Google Scholar | |
Sharma A, Mathew ME, Sriganesh V and Reiss UM: Gene therapy for haemophilia. Cochrane Database Syst Rev. 12(CD010822)2016.PubMed/NCBI View Article : Google Scholar | |
Drummond MF, Neumann PJ, Sullivan SD, Fricke FU, Tunis S, Dabbous O and Toumi M: Analytic considerations in applying a general economic evaluation reference case to gene therapy. Value Health. 22:661–668. 2019.PubMed/NCBI View Article : Google Scholar | |
Peyvandi F, Garagiola I and Young G: The past and future of haemophilia: Diagnosis, treatments, and its complications. Lancet. 388:187–197. 2016.PubMed/NCBI View Article : Google Scholar | |
Pierce GF and Coffin D: Members of the WFH Gene Therapy Round Table Program Committee and Organizing Committee. The 1st WFH gene therapy round table: Understanding the landscape and challenges of gene therapy for haemophilia around the world. Haemophilia. 25:189–194. 2019.PubMed/NCBI View Article : Google Scholar | |
Doshi BS and Arruda VR: Gene therapy for hemophilia: What does the future hold? Ther Adv Hematol. 9:273–293. 2018.PubMed/NCBI View Article : Google Scholar | |
George LA, Sullivan SK, Giermasz A, Rasko JEJ, Samelson-Jones BJ, Ducore J, Cuker A, Sullivan LM, Majumdar S, Teitel J, et al: Hemophilia B gene therapy with a high-specific-activity factor IX variant. N Engl J Med. 377:2215–2227. 2017.PubMed/NCBI View Article : Google Scholar | |
Miesbach W, Meijer K, Coppens M, Kampmann P, Klamroth R, Schutgens R, Tangelder M, Castaman G, Schwäble J, Bonig H, et al: Gene therapy with adeno-associated virus vector 5-human factor IX in adults with hemophilia B. Blood. 131:1022–1031. 2018.PubMed/NCBI View Article : Google Scholar | |
George LA, Ragni MV, Rasko JEJ, Raffini LJ, Samelson-Jones BJ, Ozelo M, Hazbon M, Runowski AR, Wellman JA, Wachtel K, et al: Long-Term follow-up of the first in human intravascular delivery of AAV for gene transfer: AAV2-hFIX16 for severe hemophilia B. Mol Ther. 28:2073–2082. 2020.PubMed/NCBI View Article : Google Scholar | |
Konkle BA, Walsh CE, Escobar MA, Josephson NC, Young G, Von Drygalski A, McPhee SWJ, Samulski RJ, Bilic I, de la Rosa M, et al: BAX 335 hemophilia B gene therapy clinical trial results: Potential impact of CpG sequences on gene expression. Blood. 137:763–774. 2021.PubMed/NCBI View Article : Google Scholar | |
Chowdary P, Shapiro S, Makris M, Evans G, Boyce S, Talks K, Dolan G, Reiss U, Phillips M, Riddell A, et al: Phase 1-2 trial of AAVS3 gene therapy in patients with hemophilia B. N Engl J Med. 387:237–247. 2022.PubMed/NCBI View Article : Google Scholar | |
Xue F, Li H, Wu X, Liu W, Zhang F, Tang D, Chen Y, Wang W, Chi Y, Zheng J, et al: Safety and activity of an engineered, liver-tropic adeno-associated virus vector expressing a hyperactive Padua factor IX administered with prophylactic glucocorticoids in patients with haemophilia B: A single-centre, single-arm, phase 1, pilot trial. Lancet Haematol. 9:e504–e513. 2022.PubMed/NCBI View Article : Google Scholar | |
Powell JS, Ragni MV, White GC II, Lusher JM, Hillman-Wiseman C, Moon TE, Cole V, Ramanathan-Girish S, Roehl H, Sajjadi N, et al: Phase 1 trial of FVIII gene transfer for severe hemophilia A using a retroviral construct administered by peripheral intravenous infusion. Blood. 102:2038–2045. 2003.PubMed/NCBI View Article : Google Scholar | |
Mahlangu J, Kaczmarek R, Von Drygalski A, Shapiro S, Chou SC, Ozelo MC, Kenet G, Peyvandi F, Wang M, Madan B, et al: Two-Year outcomes of valoctocogene roxaparvovec therapy for hemophilia A. N Engl J Med. 388:694–705. 2023.PubMed/NCBI View Article : Google Scholar |