Characteristics of BAY 2599023 in the Current Treatment Landscape of
Hemophilia A Gene Therapy

Steven   W.   Pipe; Valder   R.   Arruda; Claudia      Lange; Stephen      Kitchen; Hermann      Eichler; Samuel      Wadsworth
Abstract

Hemophilia A, a single gene disorder leading to deficient Factor VIII (FVIII), is a suitable candidate for gene therapy. The aspiration is for single administration of a genetic therapy that would allow the production of endogenous FVIII sufficient to restore hemostasis and other biological processes. This would potentially result in reliable protection from bleeding and its associated physical and emotional impacts. Gene therapy offers the possibility of a clinically relevant improvement in disease phenotype and transformational improvement in quality of life, including an opportunity to engage in physical activities more confidently. Gene therapy products for hemophilia A in advanced clinical development use adeno-associated viral (AAV) vectors and a codon-optimized B-domain deleted FVIII transgene. However, the different AAV-based gene therapies have distinct design features, such as choice of vector capsid, enhancer and promoter regions, FVIII transgene sequence and manufacturing processes. These, in turn, impact patient eligibility, safety and efficacy. Ideally, gene therapy technology for hemophilia A should offer bleed protection, durable FVIII expression, broad eligibility and limited response variability between patients, and long-term safety. However, several limitations and challenges must be overcome. Here, we introduce the characteristics of the BAY 2599023 (AAVhu37.hFVIIIco, DTX 201) gene therapy product, including the low prevalence in the general population of anti-AAV-hu37 antibodies, as well as other gene therapy AAV products and approaches. We will examine how these can potentially meet the challenges of gene therapy, with the ultimate aim of improving the lives of patients with hemophilia A.
Keywords: AAV vector, manufacturing, hemophilia A, gene therapy, treatment landscape, factor VIII, BAY 2599023.
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Graphical Abstract

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DOI https://dx.doi.org/10.2174/1566523222666220914105729	Print ISSN 1566-5232
Publisher Name Bentham Science Publisher	Online ISSN 1875-5631
Current Gene Therapy

Characteristics of BAY 2599023 in the Current Treatment Landscape of Hemophilia A Gene Therapy

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Programmed Cell Death Genes in Oncology: Pioneering Therapeutic and Diagnostic Frontiers (BMS-CGT-2024-HT-45)

Current Gene Therapy

Characteristics of BAY 2599023 in the Current Treatment Landscape of Hemophilia A Gene Therapy

Abstract

Graphical Abstract

Call for Papers in Thematic Issues

Programmed Cell Death Genes in Oncology: Pioneering Therapeutic and Diagnostic Frontiers (BMS-CGT-2024-HT-45)

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