Inflamm Bowel Dis. 2020 Sep 18;26(10):1498-1508. doi: 10.1093/ibd/izaa215.

Amy C Porter ¹, Jiri Aubrecht ², Chandler Birch ¹, Jonathan Braun ³, Carolyn Cuff ⁴, Suryasarathi Dasgupta ², Jeremy D Gale ⁵, Robert Hinton ⁶, Steven C Hoffmann ⁷, Gerard Honig ⁸, Bryan Linggi ⁹, Marco Schito ¹, Niels Vande Casteele ^10 11, John-Michael Sauer ¹

Author information

• ¹Critical Path Institute, AZ, USA.
• ²Takeda Pharmaceuticals, Cambridge, MA, USA.
• ³Cedars-Sinai Medical Center, Los Angeles, CA, USA.
• ⁴AbbVie Bioresearch Center, Worcester, MA, USA.
• ⁵Pfizer Worldwide, Research, Development and Medical, Cambridge, MA, USA.
• ⁶The David R Clare and Margaret C Clare Foundation, Morristown, NJ, USA.
• ⁷FNIH, North Bethesda, MD, USA.
• ⁸Crohn's & Colitis Foundation, New York, NY, USA.
• ⁹Robarts Clinical Trials, San Diego, CA, USA.
• ¹⁰Department of Medicine, University of California San Diego, CA, USA.
• ¹¹Robarts Clinical Trials Inc., London, ON, Canada.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.