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

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.

Principles of care for acquired hemophilia.

OBJECTIVE: To establish clear priorities for the care of patients with acquired hemophilia A (AHA) by proposing 10 key principles of practical, holistic AHA management. METHOD: These principles were developed by the Zürich Haemophilia Forum, an expert panel of European hemophilia specialists comprising physicians and nursing and laboratory specialists. RESULTS: The 10 proposed principles for AHA care are as follows: (a) Improving initial diagnosis of AHA; (b) Differential diagnosis of AHA: laboratory assessment of patients with unusual bleeding; (c) Effective communication between laboratories, physicians, and specialists; (d) Improving clinical care: networking between healthcare professionals in the treating hospital and specialist hemophilia centers; (e) Comprehensive assessment of bleeding; (f) Appropriate use of bypassing agents; (g) Long-term follow-up and monitoring for efficacy and safety of immunosuppressive treatment; (h) Inpatient/outpatient settings; (i) Access to innovative and disruptive treatments; (j) Promotion of international collaborative research. CONCLUSION: The proposed principles for holistic AHA care aim to ensure swift diagnosis and optimal patient management. Key to achieving this goal is training for healthcare personnel in non-specialist hospitals and collaboration between different specialists. We hope these principles will increase awareness of AHA in the wider medical community and catalyze efforts toward improving its practical, multidisciplinary management.

Feasibility and Results of a Mobile Haemophilia Outpatient Care Pilot Project.

INTRODUCTION: Regular visits at haemophilia treatment centres (HTCs) in rural regions are often dependent on the access to a private car due to lack of or limited availability of public means. Therefore, a mobile haemophilia outpatient care (MHOC) concept providing home visits to haemophilia patients has been developed by the Saarland HTC, which is located in a rural German region. METHODS: Haemophilia patients and their parents were home visited at least twice (baseline, follow-up) by trained medical staff. Socio-demographic and clinical data were collected and interviews were performed asking the patients and parents about their needs and expectations towards such a MHOC. RESULTS: Seventy-nine patients were enrolled (56 adults, 23 children), 62.0% severely affected, 48.1% on prophylaxis, with a mean age of 37.4 ± 16.4 years (17-78) and 9.8 ± 4.2 years (3-16), respectively. Median travel distance to the HTC was 43.5 km (3-200). Note that 92.4% considered an intense binding to the HTC and a MHOC concept as 'rather/very important' (88.6%). They expected from a MHOC to provide consulting and educating activities, support in elderhood issues and treatment. For 35.4%, a MHOC could currently provide additional support, mainly due to patient's immobility and need of consultancy. They mainly used services in terms of consultancy in social-legal affairs and support in contacting authorities. CONCLUSION: The results of this study support the hypothesis that a MHOC concept is a needful supplement in haemophilia comprehensive care and will improve the challenging haemophilia treatment, especially for those with limited access to HTCs or with disabilities.