University of Rome Tor Vergata, Rome, Italy.
Orphan Office, European Medicines Agency, Amsterdam, The Netherlands.
Br J Clin Pharmacol. 2021 Nov;87(11):4183-4196. doi: 10.1111/bcp.14838. Epub 2021 Apr 12.
Haemophilia A and B are rare bleeding disorders. Over the past decades, they have been transformed from debilitating diseases to manageable conditions in the Western world. However, optimizing haemophilia care remains challenging in developing countries. Several challenges and unmet needs remain in the treatment of the haemophilia limiting the QoL of patients. These challenges are now being addressed by extended half-life recombinant factors, rebalancing and substitution therapies. Gene therapy and genome editing show promise for a definite clinical cure. Here, we provide an overview of new therapeutic opportunities for haemophilia and their advances and limitations from a regulatory perspective. The database on human medicines from the European Medicines Agency (EMA) was used and data from rare disease (orphan) designations and EPARs were retrieved for the analysis. Clinical trial databases were used to query all active studies on haemophilia. Gene therapy medicinal products based on AAV and lentiviral vectors are in development and clinical trials have reported substantial success in ameliorating bleeding tendency in haemophilia patients. The prospect of gene editing for correction of the underlying mutation is on the horizon and has considerable potential. With regard to the benefit of the gene therapy medicinal products, more long-term efficacy and safety data are awaited. We are entering an era of innovation and abundance in treatment options for those affected by bleeding disorders, but issues remain about the affordability and accessibility to patients.
A 型和 B 型血友病都是罕见的出血性疾病。在过去的几十年中，它们已经从使人衰弱的疾病转变为西方世界可控制的疾病。然而，在发展中国家，优化血友病的护理仍然具有挑战性。在治疗血友病方面仍存在一些挑战和未满足的需求，这些因素限制了患者的生活质量。这些挑战现在通过延长半衰期的重组因子、平衡和替代疗法得到了应对。基因疗法和基因组编辑为根治血友病提供了希望。在此，我们从监管角度概述了血友病的新治疗机会及其进展和局限性。我们使用了欧洲药品管理局（EMA）的人用药品数据库，并检索了罕见病（孤儿病）指定和上市许可申请（EPAR）的数据以进行分析。临床试验数据库被用于查询所有关于血友病的正在进行的研究。基于腺相关病毒和慢病毒载体的基因治疗药物正在开发中，临床试验报告称，这些药物在改善血友病患者的出血倾向方面取得了实质性成功。基因编辑纠正潜在突变的前景即将实现，具有巨大的潜力。关于基因治疗药物的益处，还需要更多的长期疗效和安全性数据。我们正在进入一个治疗选择创新和丰富的时代，那些受出血性疾病影响的人将从中受益，但患者的负担能力和可及性仍然是一个问题。
