To provide insight into regulatory decision-making at the time of granting initial orphan designation by the Committee for Orphan Medicinal Products, we have conducted a retrospective analysis for viral vector-mediated gene therapies in rare non-oncological conditions with respect to the data provided to support the criteria to be met in successful applications. We found that a high proportion of non-clinical in vivo data was used for gene therapies, indicating earlier submissions of products that are at the stage of preclinical research and not in clinical development. Clinical data were submitted in only 13% of the applications, containing preliminary results derived from early-stage clinical trials in few patients. Mouse models were used in the majority of the submissions to generate meaningful non-clinical in vivo data highlighting their utility for proof-of-concept studies, and half of the applications containing non-clinical data generated results based solely on surrogate endpoints. The criterion of significant benefit was applicable in 54% of the submissions, which indicates that sponsors are focusing gene therapy development in areas of high unmet medical need, particularly where there are no authorized medicines available.

中文翻译：

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孤儿药名称导航：欧洲基因治疗的证据要求


为了深入了解孤儿药产品委员会授予初始孤儿药资格认定时的监管决策，我们对罕见非肿瘤疾病中的病毒载体介导的基因疗法进行了回顾性分析，分析了为支持成功申请中要满足的标准而提供的数据。我们发现，很大一部分非临床体内 数据用于基因治疗，这表明早期提交的产品处于临床前研究阶段，而不是临床开发阶段。只有 13% 的申请提交了临床数据，其中包含来自少数患者的早期临床试验的初步结果。大多数提交的内容都使用了小鼠模型来生成有意义的非临床 体内数据，突出了它们在概念验证研究中的效用，并且包含非临床数据的应用程序中的一半仅基于替代终点生成了结果。54% 的提交材料适用显著获益标准，这表明申办者将基因疗法的开发重点放在医疗需求高度未满足的领域，尤其是在没有授权药物可用的地方。