The Arrival of Gene Therapy for Patients with Hemophilia A
- PMID: 36142153
- PMCID: PMC9499514
- DOI: 10.3390/ijms231810228
The Arrival of Gene Therapy for Patients with Hemophilia A
Abstract
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.
Keywords: adeno-associated viral vector; emicizumab; exogenous factor VIII; gene therapy; hemophilia A; valoctogene roxaparvovec.
Conflict of interest statement
Giancarlo Castaman has received speaker’s fees from Bayer, Grifols, LFB, Roche, SOBI, Novo Nordisk, Werfen, and Kedrion; research funding directly from their institution from CSL Behring, Pfizer, and SOBI; and, during the last 2 years, participated in advisory boards for Bayer, BioMarin, Takeda, CSL Behring, Novo Nordisk, Pfizer, Roche, Sanofi, SOBI, and Uniqure. Raimondo De Cristofaro has received honoraria for advisory board participation from Bayer, SOBI, and Takeda. Flora Peyvandi has received honoraria for participating as a speaker at educational meetings from Grifols and Roche, and on advisory boards organized by Sanofi, SOBI, Takeda, Roche, and BioMarin. Giovanni Di Minno has received speaker’s fees from Sanofi, BioMarin, Novo Nordisk, Pfizer, Takeda, and CSL Behring. BioMarin provided funding for medical writing support for this manuscript. BioMarin had no input into the content of the manuscript. The authors take full responsibility for the drafting of this manuscript and in the final decision to publish.
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