Kerpel-Fronius Sandor, Baroutsou Varvara, Becker Sander, Carlesi Roberto, Collia Luis, Franke-Bray Brigitte, Kleist Peter, Kurihara Chieko, Laranjeira Luis Filipe, Matsuyama Kotone, Naseem Shehla, Schenk Johanna, Silva Honorio
Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
Independent Medical Consultant & Pharmaceutical Medicine Consultant, Athens, Greece.
Front Med (Lausanne). 2020 Dec 23;7:608249. doi: 10.3389/fmed.2020.608249. eCollection 2020.
Gene therapy orphan medicinal products constitute a unique group of new drugs which in case of hereditary diseases are usually administered only once at an early age, in the hope to provide sufficient gene product to last for the entire life of the patients. The combination of an exceptionally large single payment and the life-long clinical follow-up needed for understanding the long-term benefits and safety of gene therapy, represent new types of scientific, financial, social and ethical challenges for the pharmaceutical industry, regulators and society. With special consideration of the uniqueness and importance of gene therapy, the authors propose a three points plan for a close cooperation between the pharmaceutical industry and society to develop orphan gene therapy. (1) In fully transparent health technology negotiations a close and long-lasting, contractually fixed cooperation should be established between the manufacturers and local health-care stakeholders for sharing the medical and scientific benefits, the financial risks as well as the burdens of the post-authorization clinical and regulatory development. (2) The parties should agree on a fair, locally affordable drug price without the usually very high premium price calculated to compensate for the low number of patients. In case of high manufacturing costs, the companies should offer prolonged, 15-20 years long payment by installment with risk-sharing, especially considering that the late outcome of the treatment is unknown. Society should assist scientifically and financially organizing a specific patient registry, treatment in specialized hospitals and adequate long-term follow-up of patients, the coordinated management of financial transactions related to the risk sharing program. (3) The post-authorization treatment and prolonged observation of additional new cases coordinated by society should provide real world data needed for the modern complex regulatory evaluation of gene therapy products by the competent authorities. We assume that fair sharing of the benefits and risks as well as a well-organized cooperation of society with the industry in collecting real world evidence might result in better drug evaluation and improved accessibility due to lower prices. The outlined concept might support gene therapy more efficiently than the presently requested outstandingly high prices.
基因治疗孤儿药是一类独特的新药，对于遗传性疾病，通常在患者幼年时仅给药一次，以期提供足够的基因产物维持患者一生。由于理解基因治疗的长期益处和安全性需要一次性支付巨额费用以及进行终身临床随访，这给制药行业、监管机构和社会带来了新型的科学、财务、社会和伦理挑战。鉴于基因治疗的独特性和重要性，作者提出了一项三点计划，以促进制药行业与社会密切合作，开发孤儿基因治疗药物。（1）在完全透明的卫生技术谈判中，制造商与当地医疗保健利益相关者应建立密切且持久的、合同确定的合作关系，以分享医学和科学益处、财务风险以及上市后临床和监管开发的负担。（2）各方应商定一个公平的、当地可承受的药品价格，而不是通常为补偿患者数量少而计算的非常高的溢价价格。如果制造成本高，公司应提供长达15 - 20年的分期付款，并分担风险，尤其要考虑到治疗的后期结果尚不清楚。社会应在科学和财务方面协助组织特定的患者登记、专科医院的治疗以及对患者进行充分的长期随访，协调与风险分担计划相关的财务交易管理。（3）由社会协调的上市后治疗和对更多新病例的长期观察应提供主管当局对基因治疗产品进行现代复杂监管评估所需的真实世界数据。我们认为，公平分担益处和风险以及社会与行业在收集真实世界证据方面进行良好组织的合作可能会带来更好的药物评估，并因价格降低而提高可及性。所概述的概念可能比目前要求的极高价格更有效地支持基因治疗。
