TY - JOUR
T1 - The Arrival of Gene Therapy for Patients with Hemophilia A
AU - Castaman, G.
AU - Di Minno, G.
AU - De Cristofaro, Raimondo
AU - Peyvandi, F.
PY - 2022
Y1 - 2022
N2 - Historically, the standard of care for hemophilia A has been intravenous administration of exogenous factor VIII (FVIII), either as prophylaxis or episodically. The development of emicizumab, a humanized bispecific monoclonal antibody mimicking activated FVIII, was a subsequent advance in treatment. However, both exogenous FVIII and emicizumab require repeated and lifelong administration, negatively impacting patient quality of life. A recent breakthrough has been the development of gene therapy. This allows a single intravenous treatment that could result in long-term expression of FVIII, maintenance of steady-state plasma concentrations, and minimization (or possibly elimination) of bleeding episodes for the recipient’s lifetime. Several gene therapies have been assessed in clinical trials, with positive outcomes. Valoctocogene roxaparvovec (an adeno-associated viral 5-based therapy encoding human B domain-deleted FVIII) is expected to be the first approved gene therapy in European countries, including Italy, in 2022. Some novel challenges exist including refining patient selection criteria, managing patient expectations, further elucidation of the durability and variability of transgene expression and long-term safety, and the development of standardized ‘hub and spoke’ centers to optimize and monitor this innovative treatment. Gene therapy represents a paradigm shift, and may become a new reference standard for treating patients with hemophilia A.
AB - Historically, the standard of care for hemophilia A has been intravenous administration of exogenous factor VIII (FVIII), either as prophylaxis or episodically. The development of emicizumab, a humanized bispecific monoclonal antibody mimicking activated FVIII, was a subsequent advance in treatment. However, both exogenous FVIII and emicizumab require repeated and lifelong administration, negatively impacting patient quality of life. A recent breakthrough has been the development of gene therapy. This allows a single intravenous treatment that could result in long-term expression of FVIII, maintenance of steady-state plasma concentrations, and minimization (or possibly elimination) of bleeding episodes for the recipient’s lifetime. Several gene therapies have been assessed in clinical trials, with positive outcomes. Valoctocogene roxaparvovec (an adeno-associated viral 5-based therapy encoding human B domain-deleted FVIII) is expected to be the first approved gene therapy in European countries, including Italy, in 2022. Some novel challenges exist including refining patient selection criteria, managing patient expectations, further elucidation of the durability and variability of transgene expression and long-term safety, and the development of standardized ‘hub and spoke’ centers to optimize and monitor this innovative treatment. Gene therapy represents a paradigm shift, and may become a new reference standard for treating patients with hemophilia A.
KW - adeno-associated viral vector
KW - emicizumab
KW - valoctogene roxaparvovec
KW - gene therapy
KW - hemophilia A
KW - exogenous factor VIII
KW - adeno-associated viral vector
KW - emicizumab
KW - valoctogene roxaparvovec
KW - gene therapy
KW - hemophilia A
KW - exogenous factor VIII
UR - http://hdl.handle.net/10807/303917
U2 - 10.3390/ijms231810228
DO - 10.3390/ijms231810228
M3 - Article
SN - 1422-0067
VL - 23
SP - N/A-N/A
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
ER -