Kakkis Emil D, O'Donovan Mary, Cox Gerald, Hayes Mark, Goodsaid Federico, Tandon P K, Furlong Pat, Boynton Susan, Bozic Mladen, Orfali May, Thornton Mark
EveryLife Foundation for Rare Diseases, Novato, CA, USA.
BioMarin Pharmaceutical Inc., Novato, CA, USA.
Orphanet J Rare Dis. 2015 Feb 10;10:16. doi: 10.1186/s13023-014-0195-4.
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.
对于罕见的严重和危及生命的疾病，将科学发现转化为新的药物治疗面临着巨大挑战。这一挑战已得到所有利益相关者的认可，他们赞同在新型疗法治疗罕见疾病的监管审查过程中需要灵活性。在美国，这种灵活性的最佳体现是创建了加速批准（AA）途径。AA途径对于开发满足未满足医疗需求的疾病治疗方法至关重要，并已广泛用于治疗癌症和艾滋病等传染病的药物。2012年，AA条款进行了修订，以加强AA途径的应用，加快根据《食品药品监督管理局安全与创新法案》（FDASIA）开发用于罕见疾病的药物。FDASIA在众多条款中要求制定一份更具相关性的FDA指南，说明支持使用新型替代终点可能可接受的证据类型。将AA应用于罕见疾病需要更高的可预测性，以推动更多可能无法开发出来的罕见疾病治疗方法更广泛地获得并合理使用AA。本白皮书提出了一个评估生物标志物终点的科学框架，以加强针对目前尚无充分治疗方法的罕见和毁灭性疾病的新型疗法的开发，该框架基于药物开发专家和罕见疾病患者群体的意见。具体建议包括：1）为罕见疾病项目增加AA途径的使用建立监管依据；2）实施生物标志物资格认定申请程序，以便有机会尽早确定生物标志物是否可接受；3）提出将生物标志物鉴定为主要终点的科学框架。本文最后一部分重点介绍了成功案例，这些案例已将生物标志物终点纳入FDA对罕见疾病疗法的批准中。本文重点关注美国的情况，但这些建议合理适用于任何司法管辖区。
