Patient selection for hemophilia gene therapy: Real‐life data from a single center

Krumb, Evelien; Lambert, Catherine; Hermans, Cédric

doi:10.1002/rth2.12494

Cited by 13 publications

(15 citation statements)

References 11 publications

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“…In a single-centre study conducted in our haemophilia clinic in Brussels, there were 87 adult patients with severe HA or HB. 39 Of these, most individuals with severe haemophilia could not be enrolled, almost half due to partly modifiable psychosocial reasons (49.4%). Of note is that the number of patients who would accept gene therapy in the absence of strict clinical trial requirements was estimated at 36 (41.4%), irrespective of any exclusion criteria.…”

Section: Requirements For Implementing Gene Therapymentioning

confidence: 99%

How to translate and implement the current science of gene therapy into haemophilia care?

Hermans

Gruel

Frenzel

et al. 2023

Therapeutic Advances in Hematology

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Gene-based therapy opens an entirely new paradigm in managing people with haemophilia (PWH), offering them the possibility of a functional cure by enabling continuous expression of factor VIII (FVIII) or factor IX (FIX) after transfer of a functional gene designed to replace the PWH’s own defective gene. In recent years, significant advances in gene therapy have been made, resulting in clotting factor activity attaining near-normal levels, as reflected by ‘zero bleeding rates’ in previously severely inflicted patients following a single administration of adeno-associated viral (AAV) vectors. While this new approach represents a major advancement, there are still several issues that must be resolved before applying this technology in clinical practice. First, awareness, communication, and education about the therapeutic potential and modalities of gene therapy must be further strengthened. To this end, objective, unbiased, transparent, and regularly updated information must be shared, in an appropriate way and understandable language with the support of patients’ organizations. Second, healthcare providers should adopt a patient-centred approach, as the ‘one size fits all’ approach is inappropriate when considering gene therapy. Instead, a holistic patient view taking into account their physical and mental dimensions, along with unexpressed expectations and preferences, is mandatory. Third, the consent procedure must be improved, ensuring that patients’ interests are maximally protected. Finally, gene therapy is likely to be first delivered in a few centres, with the highest expertise and experience in this domain. Thus, patients should be managed based on a hub-and-spoke model, taking into account that the key to gene therapy’s success lies in an optimal communication and collaboration both within and between haemophilia centres sharing their experiences in the frame of international registries. This review describes recent progress and explains outstanding hurdles that must be tackled to ease the implementation of this paradigm-changing new therapy.

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Section: Requirements For Implementing Gene Therapymentioning

confidence: 99%

How to translate and implement the current science of gene therapy into haemophilia care?

Hermans

Gruel

Frenzel

et al. 2023

Therapeutic Advances in Hematology

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“…73,74 The education material must also address the psychosocial burden on the participant, which may affect a patient's willingness to undergo gene therapy. 75 Multiple guidelines are published on how to discuss gene therapy with patients, provide lists of helpful vocabulary or pictorial representation of the basic process of gene therapy, and highlight topics of discussion related to safety and efficacy. [76][77][78] These tools can help guide face-to-face discussions with each patient and should be individualized based on their priorities and fears (Table 3).…”

Section: Dovepressmentioning

confidence: 99%

Gene Therapy and Hemophilia: Where Do We Go from Here?

Bolous¹,

Bhatt²,

Bhakta³

et al. 2022

JBM

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Gene therapy for hemophilia using adeno-associated virus (AAV) derived vectors can reduce or eliminate patients’ disease-related complications and improve their quality of life. Broad implementation globally will lead to societal gains and foster health equity. Several vector products each for factor IX (FIX) or factor VIII (FVIII) deficiency are in advanced clinical development. Safety data are reassuring. Efficacy data for up to 8 and 5 years, respectively, vary considerably among vector types and among individuals, but indicate significant reduction in bleeds and factor use. Products will soon be approved for marketing. This review highlights the relevant considerations for implementation of hemophilia gene therapy, specifically across a broad range of socioeconomic backgrounds globally, based on recent publications and our own experience. We address the current efficacy and safety data and relevant aspects of vector immunology. We then discuss pertinent implementation steps including pre-implementation and readiness assessments, considerations on cost, cost-effectiveness and payment models, approaches to education and informed consent, and the operational needs as well as the need for monitoring of health outcomes and implementation outcomes. To prevent a lag or complete lack of establishing access to this life-changing therapy option for all patients with hemophilia worldwide, adaptable pathways supported by collaborative and international efforts of all stakeholders are needed.

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“… 61 , 62 While the intensity of patient monitoring may reduce outside of trials, regular tests will still be essential, particularly to detect any liver abnormalities. 61 , 63 Gene therapy recipients will be encouraged to provide informed consent to participate in the WFH GTR, although the process has not yet been defined. 61 , 62 The development of tools to reinforce patients’ commitment to follow-up has been proposed, 61 and engagement activities to inform HCPs and PwH about the importance of health-surveillance have already started.…”

Section: Informed Consent In Haemophilia Gene Therapymentioning

confidence: 99%

Improving patient informed consent for haemophilia gene therapy: the case for change

Woollard¹,

Gorman

Rosenfelt

2021

Therapeutic Advances in Rare Disease

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Adeno-associated virus-based gene therapy points to a coming transformation in the treatment of people living with haemophilia, promising sustained bleed control and potential improvement in quality of life. Nevertheless, the consequences of introducing new genetic material are not trivial. The perceived benefits should not minimise the challenges facing patients in understanding the long-term risks and providing a valid and meaningful informed consent, whether in a research or clinical setting. Informed consent is a fundamentally important doctrine in both medical ethics and health law, upholding an individual’s right to define their personal goals and make their own autonomous choices. Patients should be enabled to recognise their clinical situation, understand the implications of treatment and integrate every facet of their life into their decision. This review describes informed consent processes for haemophilia gene therapy clinical trials, factors affecting patients’ decision making and the availability of patient-centred decision support interventions, to ensure that patients’ interests are being protected. Regulatory guidance has been published for physicians and manufacturers in haemophilia on informed consent, including for gene therapy, while best-practice recommendations for patient–physician discussions are available. In all settings, however, communicating and presenting highly technical and complex therapeutic information is challenging, especially where multiple barriers to scientific knowledge and health literacy exist. We propose several evidence-informed strategies to enhance the consent procedure, such as utilising validated literacy and knowledge assessment tools as well as participatory learning environments over an extended period, to ensure that patients are fully cognisant of the consent they give or deny. Further research is needed to define new, creative approaches for patient education and the upholding of ethical values in the informed consent process for gene therapy. The lessons learnt and approaches developed within haemophilia could set the gold standard for good practice in ensuring ethical preparedness amidst advances in genetic therapies. Plain language summary Improving the informed consent process for people living with haemophilia considering gene therapy. Gene therapy is the process of replacing faulty genes with healthy ones. In haemophilia, gene therapy involves introducing a working copy of the gene for the clotting factor that patients are missing. Following treatment, patients should begin producing their own clotting factor normally. However, people living with haemophilia (PwH) need to be fully informed regarding the potential benefits and risks of gene therapy and what this means for them, whether as part of a research study or routine medical care. Patients must be respected and supported to make decisions about their own health and wellbeing, recognising their legal and moral right to set personal goals and make treatment choices. For this to happen in practice, patients should be aware of their individual health needs, understand the effects of treatment and consider lifestyle preferences in relation to their decisions. This article attempts to describe how informed consent is obtained in haemophilia gene therapy clinical trials, what affects a patient’s ability to make decisions and the availability of information and support to respect and protect the interests of PwH. Regulators responsible for approving medical products have published guidance on informed consent for physicians and pharmaceutical manufacturers in haemophilia, including for gene therapy. Recommendations have been made about the best ways for PwH to discuss gene therapy with their physicians. Yet, poor communication of complex topics, such as gene therapy, can be problematic, especially if patients lack the skills and confidence to understand and discuss the science, or for physicians with limited time in clinic. We propose strategies to improve the consent process, so patients can feel more able to make informed decisions about new treatments. Further research is needed to find new, creative approaches for educating patients and ensuring that the informed consent process for gene therapy in haemophilia is ethical.

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Patient selection for hemophilia gene therapy: Real‐life data from a single center

Cited by 13 publications

References 11 publications

How to translate and implement the current science of gene therapy into haemophilia care?

How to translate and implement the current science of gene therapy into haemophilia care?

Gene Therapy and Hemophilia: Where Do We Go from Here?

Improving patient informed consent for haemophilia gene therapy: the case for change

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