Critical Path Institute, AZ, USA.
Takeda Pharmaceuticals, Cambridge, MA, USA.
Inflamm Bowel Dis. 2020 Sep 18;26(10):1498-1508. doi: 10.1093/ibd/izaa215.
Currently, 2 coprimary end points are used by health authorities to determine the effectiveness of therapeutic interventions in patients with Crohn's disease (CD): symptomatic remission (patient-reported outcome assessment) and endoscopic remission (ileocolonoscopy). However, there is lack of accepted biomarkers to facilitate regulatory decision-making in the development of novel therapeutics for the treatment of CD.
With support from the Helmsley Charitable Trust, Critical Path Institute formed the Crohn's Disease Biomarkers preconsortium (CDBpC) with members from the pharmaceutical industry, academia, and nonprofit organizations to evaluate the CD biomarker landscape. Biomarkers were evaluated based on biological relevance, availability of biomarker assays, and clinical validation data.
The CDBpC identified the most critical need as pharmacodynamic/response biomarkers to monitor disease activity in response to therapeutic intervention. Fecal calprotectin (FC) and serum C-reactive protein (CRP) were identified as biomarkers ready for the regulatory qualification process. A number of exploratory biomarkers and potential panels of these biomarkers was also identified for additional development. Given the different factors involved in CD and disease progression, a combination of biomarkers, including inflammatory, tissue injury, genetic, and microbiome-associated biomarkers, will likely have the most utility.
The primary focus of the Inflammatory Bowel Disease Regulatory Science Consortium will be development of exploratory biomarkers and the qualification of FC and CRP for IBD. The Inflammatory Bowel Disease Regulatory Science Consortium, focused on tools to support IBD drug development, will operate in the precompetitive space to share data, biological samples for biomarker testing, and assay information for novel biomarkers.
目前，卫生当局使用 2 个主要终点来确定克罗恩病（CD）患者治疗干预的有效性：症状缓解（患者报告的结果评估）和内镜缓解（回结肠镜检查）。然而，缺乏被接受的生物标志物来促进新型治疗药物开发的监管决策。
在 Helmsley 慈善信托基金会的支持下，关键路径研究所（CPCI）与制药行业、学术界和非营利组织的成员组成了克罗恩病生物标志物前联盟（CDBpC），以评估 CD 生物标志物领域。生物标志物是根据生物学相关性、生物标志物检测的可用性和临床验证数据进行评估的。
CDBpC 确定了最关键的需求，即监测治疗干预后疾病活动的药效/反应生物标志物。粪便钙卫蛋白（FC）和血清 C 反应蛋白（CRP）被确定为可用于监管资格认证过程的生物标志物。还确定了一些探索性生物标志物及其潜在的生物标志物组合，用于进一步开发。鉴于 CD 和疾病进展涉及的不同因素，包括炎症、组织损伤、遗传和微生物组相关的生物标志物在内的组合可能具有最大的效用。
炎症性肠病监管科学联盟的主要重点将是开发探索性生物标志物，并为 IBD 确定 FC 和 CRP 的资格。炎症性肠病监管科学联盟专注于支持 IBD 药物开发的工具，将在竞争前空间运作，以共享数据、用于生物标志物测试的生物样本以及用于新型生物标志物的检测信息。
