The evolving landscape of gene therapy for congenital haemophilia: An unprecedented, problematic but promising opportunity for worldwide clinical studies

With liver-directed gene therapy, congenital haemophilia has the potential to progress from an incurable to a phenotypically curable condition. However, the proportion of haemophilia population likely to benefit from gene therapy remains to be established. Achieving a phenotypic curative goal is presently hampered by: 1) availability of effective treatments (e.g. extended half-life products, non-factor therapies) that address major unmet needs in haemophilia; 2) key differences between hope and reality that patients undergoing gene therapy face (e.g. unknown risks and long-term follow-up, durability of the therapeutic effect, possibility of re-administering the vector), 3) lack of expertise of health care professionals (HCP) in managing/monitoring unexpected side effects in patients, and 4) lack of expertise of HCP in advising payers on key issues for cost-effectiveness analyses of gene therapy (e.g., eligibility criteria, predictability of response, unknown risks, long-term complications). There is also uncertainty about the possibility to absorb the cost of the “one-time, one-dose cure” by payers that are used to different payment models. An active partnership between regulators, payers, patients and health care professionals is key to identify patient sub-populations that might benefit the most from gene therapy, and to align the interests of patients (needing effective disease correction and improved quality of life) and pharma companies (reluctant to lose the profitability of lifelong repeated treatments). Educational programs will provide the healthcare chain with information on the strategy that is expected to transform morbidity and mortality patterns and how it should be regarded as part of the future therapeutic options in haemophilia.