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Review
. 2022 Oct 6:13:559-580.
doi: 10.2147/JBM.S371438. eCollection 2022.

Gene Therapy and Hemophilia: Where Do We Go from Here?

Nancy S Bolous  1 , Nidhi Bhatt  2 , Nickhill Bhakta  1 , Ellis J Neufeld  2 , Andrew M Davidoff  3 , Ulrike M Reiss  2
Affiliations
Review

Gene Therapy and Hemophilia: Where Do We Go from Here?

Nancy S Bolous et al. J Blood Med. .

Abstract

Gene therapy for hemophilia using adeno-associated virus (AAV) derived vectors can reduce or eliminate patients' disease-related complications and improve their quality of life. Broad implementation globally will lead to societal gains and foster health equity. Several vector products each for factor IX (FIX) or factor VIII (FVIII) deficiency are in advanced clinical development. Safety data are reassuring. Efficacy data for up to 8 and 5 years, respectively, vary considerably among vector types and among individuals, but indicate significant reduction in bleeds and factor use. Products will soon be approved for marketing. This review highlights the relevant considerations for implementation of hemophilia gene therapy, specifically across a broad range of socioeconomic backgrounds globally, based on recent publications and our own experience. We address the current efficacy and safety data and relevant aspects of vector immunology. We then discuss pertinent implementation steps including pre-implementation and readiness assessments, considerations on cost, cost-effectiveness and payment models, approaches to education and informed consent, and the operational needs as well as the need for monitoring of health outcomes and implementation outcomes. To prevent a lag or complete lack of establishing access to this life-changing therapy option for all patients with hemophilia worldwide, adaptable pathways supported by collaborative and international efforts of all stakeholders are needed.

Keywords: adeno-associated virus vector; cost-effectiveness; factor IX; factor VIII; global health; health equity.

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Conflict of interest statement

NB receives research support from Pfizer. EJN has served on advisory boards for BioMarin, Genentech, Novo Nordisk and Octapharma, and on data monitoring boards for Merck, Agios and Sobi; was consultant to Pfizer and Bayer, and has received honoraria from Octapharma, Novo Nordisk and Takeda. AMD has contributed to the design of the shortened LP1 promoter of the scAAV2/8-FIX-Padua vector and is entitled to receive a share of net license income if this vector is commercialized. He also reports a patent design of gene therapy vectors for producing FVIII, FIX licensed to BioMarin, a patent design of gene therapy vectors for producing FVIII, FIX licensed to UniQure. UMR receives resaerch support from Pfizer. The other authors report no conflicts of interest in this work.

References

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