Recommendations for the development of rare disease drugs using the accelerated approval pathway and for qualifying biomarkers as primary endpoints.
Recommendations for the development of rare disease drugs using the accelerated approval pathway and for qualifying biomarkers as primary endpoints.
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DOI：
10.1186/s13023-014-0195-4
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发表时间：
2015-02-10
影响因子：
3.7
通讯作者：
Thornton M
中科院分区：
文献类型：
--
作者：
Kakkis ED;O'Donovan M;Cox G;Hayes M;Goodsaid F;Tandon PK;Furlong P;Boynton S;Bozic M;Orfali M;Thornton M
对于罕见的严重且危及生命的疾病，将科学发现转化为新的药物治疗面临着巨大的挑战。这一挑战已得到所有利益相关者的认可，他们赞同治疗罕见疾病的新疗法的监管审查过程需要灵活性。在美国，这种灵活性的最佳体现是加速审批（AA）途径的创建。 AA 途径对于医疗需求未得到满足的疾病治疗方法的开发至关重要，并已广泛用于治疗癌症和艾滋病毒等传染病的药物。 2012 年，对 AA 条款进行了修订，以加强 AA 途径的应用，以加快美国食品药品监督管理局安全与创新法案 (FDASIA) 下罕见疾病药物的开发。 FDASIA 的众多条款中，要求就可以接受的证据类型制定更相关的 FDA 指南，以支持使用新的替代终点。 AA 在罕见疾病中的应用需要更高的可预测性，以推动更多人适当使用 AA 来治疗更多罕见疾病，否则这些治疗可能无法开发。本白皮书基于药物开发专家和罕见病患者群体的意见，提出了一个评估生物标志物终点的科学框架，以促进目前尚未得到充分治疗的罕见和毁灭性疾病的新疗法的开发。具体建议包括： 1) 建立在罕见疾病项目中增加 AA 获取的监管理由； 2) 实施生物标志物资格申请流程，为及早确定生物标志物的接受度提供机会； 3) 拟议的将生物标志物限定为主要终点的科学框架。该论文的最后部分重点介绍了将生物标志物终点纳入 FDA 批准的罕见疾病治疗的成功案例的案例研究。本文的重点是美国的情况，但建议合理地适用于任何司法管辖区。本文的在线版本 (doi:10.1186/s13023-014-0195-4) 包含补充材料，可供授权用户使用。
For rare serious and life-threatening disorders, there is a tremendous challenge of transforming scientific discoveries into new drug treatments. This challenge has been recognized by all stakeholders who endorse the need for flexibility in the regulatory review process for novel therapeutics to treat rare diseases. In the United States, the best expression of this flexibility was the creation of the Accelerated Approval (AA) pathway. The AA pathway is critically important for the development of treatments for diseases with high unmet medical need and has been used extensively for drugs used to treat cancer and infectious diseases like HIV. In 2012, the AA provisions were amended to enhance the application of the AA pathway to expedite the development of drugs for rare disorders under the Food and Drug Administration Safety and Innovation Act (FDASIA). FDASIA, among many provisions, requires the development of a more relevant FDA guidance on the types of evidence that may be acceptable in support of using a novel surrogate endpoint. The application of AA to rare diseases requires more predictability to drive greater access to appropriate use of AA for more rare disease treatments that might not be developed otherwise. This white paper proposes a scientific framework for assessing biomarker endpoints to enhance the development of novel therapeutics for rare and devastating diseases currently without adequate treatment and is based on the opinions of experts in drug development and rare disease patient groups. Specific recommendations include: 1) Establishing regulatory rationale for increased AA access in rare disease programs; 2) Implementing a Biomarker Qualification Request Process to provide the opportunity for an early determination of biomarker acceptance; and 3) A proposed scientific framework for qualifying biomarkers as primary endpoints. The paper’s final section highlights case studies of successful examples that have incorporated biomarker endpoints into FDA approvals for rare disease therapies. The focus of this paper is on the situation in the Unites States, but the recommendations are reasonably applicable to any jurisdiction. The online version of this article (doi:10.1186/s13023-014-0195-4) contains supplementary material, which is available to authorized users.
影响因子：
9.7
作者：
Fleming, TR
通讯作者：
Fleming, TR
影响因子：
3.7
作者：
Miyamoto BE;Kakkis ED
通讯作者：
Kakkis ED