• Wolfgang Miesbach, Robert Klamroth, Johannes Oldenburg, and Andreas Tiede.
• Department of Haemostaseology and Hemophilia Center, Medical Clinic 2, Institute of Transfusion Medicine, University Hospital Frankfurt, Frankfurt am Main; Department for Internal Medicine, Vascular Medicine and Haemostaseology, Vivantes Klinikum im Friedrichshain, Berlin; Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn; Department of Hematology, Hemostaseology, Oncology and Stem Cell Transplantation, Hannover Medical School.
• Dtsch Arztebl Int. 2022 Dec 27; 119 (51-52): 887894887-894.

BackgroundAAV (adeno-associated virus)-based gene therapy is a new treatment for hemophilia and has recently received approval for the treatment of severe hemophilia A. It does not suffer from the limitations of the current standard treatment (regular prophylactic intravenous injections of the missing clotting factor; subcutaneous injection of a bispecific antibody in hemophilia A) and can, it is hoped, raise the concentration of the missing clotting factor over the long term. AAV-based gene therapy can only be performed once, however, because of the generation of antibodies to AAV.MethodsThis review is based on publications retrieved by a selective search in the MEDLINE/PubMed database employing the relevant key words, supplemented by expert opinions and the recommendations of the relevant medical societies.ResultsData from non-randomized phase 1 to phase 3 trials reveal an adequate expression of factors VIII and IX in patients with mostly severe hemophilia A or B. Even though they were no longer receiving prophylactic treatment, most patients experienced a considerable reduction, by 53% to 96%, in the number of bleedings compared to previous therapy. Persistently elevated factor levels have been described for up to six years in hemophilia A and up to eight years in hemophilia B. The most common side effect of gene therapy is an inflammatory response with elevated alanine aminotransferase levels (17% to 89%, depending on the study), which may be associated with a reduced clotting factor level and requires treatment with transient immunosuppression.ConclusionGene therapy for hemophilia holds out the prospect of freedom from hemorrhage without the need for regular treatment with drugs. The various steps that need to be carried out in gene therapy should be coordinated in a graded and partly overlapping integrated care model (a so-called hub-and-spoke model). Electronic platforms should be used for data acquisition and transmission.

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