Amicus Therapeutics, Inc., 1 Cedar Brook Drive, Cranbury, NJ, 08512, USA.
Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ, 07936, USA.
Orphanet J Rare Dis. 2019 Feb 8;14(1):36. doi: 10.1186/s13023-019-1017-5.
Rare or orphan diseases often are inherited and overwhelmingly affect children. Many of these diseases have no treatments, are incurable, and have a devastating impact on patients and their families. Regulatory standards for drug approval for rare diseases must ensure that patients receive safe and efficacious treatments. However, regulatory bodies have shown flexibility in applying these standards to drug development in rare diseases, given the unique challenges that hinder efficient and effective traditional clinical trials, including low patient numbers, limited understanding of disease pathology and progression, variability in disease presentation, and a lack of established endpoints.To take steps toward improving rare disease clinical development strategies under current global regulatory statutes, Amicus Therapeutics, Inc. and BioNJ convened a 1-day meeting that included representatives from the Food and Drug Administration (FDA), biopharmaceutical industry, and not-for-profit agencies. The meeting focused on orphan diseases in pediatric and adult patients and was intended to identify potential strategies to overcome regulatory hurdles through open collaboration.During this meeting, several strategies were identified to minimize the limitations associated with low patient numbers in rare diseases, including the use of natural history to generate historical control data in comparisons, simulations, and identifying inclusion/exclusion criteria and appropriate endpoints. Novel approaches to clinical trial design were discussed to minimize patient exposure to placebo and to reduce the numbers of patients and clinical trials needed for providing substantial evidence. Novel statistical analysis approaches were also discussed to address the inherent challenges of small patient numbers. Areas of urgent unmet need were identified, including the need to develop registries that protect patient identities, to establish close collaboration and communication between the sponsor and regulatory bodies to address methodological and statistical challenges, to collaborate in pre-competitive opportunities within multiple sponsors and in conjunction with academia and disease-specific patient advocacy groups for optimal data sharing, and to develop harmonized guidelines for data extrapolation from source to target pediatric populations. Ultimately, these innovations will help in solving many regulatory challenges in rare disease drug development and encourage the availability of new treatments for patients with rare diseases.
罕见病或孤儿病通常是遗传性的，绝大多数影响儿童。许多此类疾病尚无治疗方法，无法治愈，会对患者及其家庭造成毁灭性影响。用于罕见病药物审批的监管标准必须确保患者获得安全有效的治疗。然而，鉴于阻碍传统临床试验高效和有效进行的独特挑战，包括患者数量少、对疾病病理和进展的了解有限、疾病表现的可变性以及缺乏既定的终点，监管机构在为罕见病药物开发应用这些标准方面表现出了灵活性。为了根据当前全球监管法规采取措施改进罕见病临床开发策略，Amicus Therapeutics, Inc. 和 BioNJ 召开了为期 1 天的会议，会议邀请了来自美国食品和药物管理局（FDA）、生物制药行业和非营利机构的代表。会议重点关注儿科和成年患者的罕见病，并旨在确定通过公开合作克服监管障碍的潜在策略。在这次会议上，确定了几种策略来最小化罕见病中患者数量少带来的限制，包括利用自然史在比较、模拟中生成历史对照数据，以及确定纳入/排除标准和适当的终点。会上还讨论了临床试验设计的新方法，以尽量减少患者接触安慰剂的情况，并减少为提供充分证据所需的患者数量和临床试验数量。会上还讨论了新的统计分析方法，以解决患者数量少带来的固有挑战。会上确定了急需解决的未满足需求领域，包括开发保护患者身份的登记处，建立赞助方和监管机构之间的密切合作和沟通，以解决方法学和统计方面的挑战，在多个赞助方和学术界以及特定疾病患者倡导团体内部合作，进行竞争前的机会，以实现最佳数据共享，以及制定从源人群到目标儿科人群的数据外推的协调准则。最终，这些创新将有助于解决罕见病药物开发中的许多监管挑战，并鼓励为罕见病患者提供新的治疗方法。
