Evolving Concepts in Phases I and II Drug Development for Crohn's Disease

Vipul Jairath; Barrett G Levesque; Niels Vande Casteele; Reena Khanna; Mahmoud Mosli; Pieter Hindryckx; Simon Travis; Marjolijn Duijvestein; Jordi Rimola; Julian Panes; Geert D'Haens; William J Sandborn; Brian G Feagan

doi:10.1093/ecco-jcc/jjw137

Evolving Concepts in Phases I and II Drug Development for Crohn's Disease

J Crohns Colitis. 2017 Feb;11(2):246-255. doi: 10.1093/ecco-jcc/jjw137. Epub 2016 Aug 3.

Authors

Vipul Jairath^{1

2

3}, Barrett G Levesque^{2

4}, Niels Vande Casteele^{2

4

5}, Reena Khanna^{1

2}, Mahmoud Mosli⁶, Pieter Hindryckx^{2

7}, Simon Travis³, Marjolijn Duijvestein⁸, Jordi Rimola⁹, Julian Panes⁹, Geert D'Haens^{2

8}, William J Sandborn^{2

4}, Brian G Feagan^{10

2

11}

Affiliations

¹ Department of Medicine, University of Western Ontario, London, ON, Canada.
² Robarts Clinical Trials Inc., Robarts Research Institute, University of Western Ontario, London, ON, Canada.
³ Nufﬁeld Department of Experimental Medicine, University of Oxford, Oxford, UK.
⁴ Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA.
⁵ KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium.
⁶ Department of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
⁷ University Hospital of Ghent, Ghent, Belgium.
⁸ Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, The Netherlands.
⁹ Hospital Clinic of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.
¹⁰ Department of Medicine, University of Western Ontario, London, ON, Canada brian.feagan@robartsinc.com.
¹¹ Department of Epidemiology and Biostatistics, University of Western Ontario, London, ON, Canada.

PMID: 27487793
DOI: 10.1093/ecco-jcc/jjw137

Abstract

The highest attrition rates during drug development programmes occur at the proof of concept stage. Given the large number of molecules under development for Crohn's disease, a need exists to improve the efficiency of early drug development by fast-tracking promising agents and terminating ineffective ones. Multiple opportunities are available to achieve these goals, including the use of more responsive outcome measures, and the incorporation of sophisticated pharmacokinetic modelling and/or highly specific pharmacodynamic markers into exposure-based dosing regimens and novel trial designs. In this article we review these strategies and propose an integrated paradigm of early drug development in Crohn's disease.

Keywords: Crohn’s disease; clinical trials.

Publication types

Review

MeSH terms

Crohn Disease / drug therapy*
Drug Approval / organization & administration*
Drug Discovery / methods
Gastrointestinal Agents* / classification
Gastrointestinal Agents* / pharmacology
Humans
Treatment Outcome

Substances

Gastrointestinal Agents