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  • Perspective
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Navigating the complexities of drug development for inflammatory bowel disease

Nature Reviews Drug Discovery volume 23, pages 546–562 (2024)Cite this article

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Abstract

Inflammatory bowel disease (IBD) — consisting of ulcerative colitis and Crohn’s disease — is a complex, heterogeneous, immune-mediated inflammatory condition with a multifactorial aetiopathogenesis. Despite therapeutic advances in this arena, a ceiling effect has been reached with both single-agent monoclonal antibodies and advanced small molecules. Therefore, there is a need to identify novel targets, and the development of companion biomarkers to select responders is vital. In this Perspective, we examine how advances in machine learning and tissue engineering could be used at the preclinical stage where attrition rates are high. For novel agents reaching clinical trials, we explore factors decelerating progression, particularly the decline in IBD trial recruitment, and assess how innovative approaches such as reconfiguring trial designs, harmonizing end points and incorporating digital technologies into clinical trials can address this. Harnessing opportunities at each stage of the drug development process may allow for incremental gains towards more effective therapies.

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Fig. 1: Challenges and opportunities for IBD drug development.
Fig. 2: Innovative study designs to improve efficiency for IBD drug development.

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Authors and Affiliations

  1. Department of Gastroenterology, St George’s University Hospitals NHS Foundation Trust, London, UK

    Sailish Honap

  2. School of Immunology and Microbial Sciences, King’s College London, London, UK

    Sailish Honap

  3. INFINY Institute, Nancy University Hospital, Vandœuvre-lès-Nancy, France

    Sailish Honap & Laurent Peyrin-Biroulet

  4. Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University, London, Ontario, Canada

    Vipul Jairath

  5. Lawson Health Research Institute, Western University, London, Ontario, Canada

    Vipul Jairath

  6. Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada

    Vipul Jairath

  7. Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy

    Silvio Danese

  8. Department of Gastroenterology, Nancy University Hospital, Vandœuvre-lès-Nancy, France

    Laurent Peyrin-Biroulet

  9. INSERM, NGERE, University of Lorraine, Nancy, France

    Laurent Peyrin-Biroulet

  10. FHU-CURE, Nancy University Hospital, Vandœuvre-lès-Nancy, France

    Laurent Peyrin-Biroulet

  11. Groupe Hospitalier privé Ambroise Paré — Hartmann, Paris IBD Center, Neuilly sur Seine, France

    Laurent Peyrin-Biroulet

  12. Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada

    Laurent Peyrin-Biroulet

Authors
  1. Sailish Honap
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  2. Vipul Jairath
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  3. Silvio Danese
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  4. Laurent Peyrin-Biroulet
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Contributions

All authors contributed to the development of presented concepts and writing of the manuscript.

Corresponding authors

Correspondence to Sailish Honap or Laurent Peyrin-Biroulet.

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Competing interests

S.H. served as a speaker, a consultant, an advisory board member and/or has received travel grants from Pfizer, Janssen, AbbVie, Takeda, Ferring and Pharmacosmos. V.J. has received consulting/advisory board fees from AbbVie, Alimentiv Inc., Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, AstraZeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus, Reistone Biopharma, Roche, Sandoz, Second Genome, Sorriso Pharmaceuticals, Takeda, Teva, Topivert, Ventyx and Vividion; and speaker fees from AbbVie, Ferring, Bristol Myers Squibb, Galapagos, Janssen, Pfizer, Shire, Takeda and Fresenius Kabi. S.D. has served as a speaker, consultant and advisory board member for Schering-Plough, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson and Johnson, Millenium Takeda, MSD, Nikkiso Europe GmbH, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB Pharma and Vifor. L.P.-B. reports consulting fees from AbbVie, Abivax, Adacyte, Alimentiv, Amgen, Applied Molecular Transport, Arena, Banook, Biogen, Bristol Myers Squibb, Celltrion, Connect Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, IAC Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeuthics, Pandion Therapeuthics, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Samsung, Sandoz, Sanofi, Satisfay, Takeda, Telavant, Theravance, Thermo Fischer, Tigenix, Tillots, Viatris, Vectivbio, Ventyx and Ysopia; grants from Celltrion, Fresenius Kabi, Medac, MSD and Takeda; lecture fees from AbbVie, Amgen, Arena, Biogen, Celltrion, Ferring, Galapagos, Genentech, Gilead, Janssen, Lilly, Medac, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda, Tillots and Viatris; and travel support from AbbVie, Amgen, Celltrion, Connect Biopharm, Ferring, Galapagos, Genentech, Gilead, Gossamer Bio, Janssen, Lilly, Medac, Morphic, MSD, Pfizer, Sandoz, Takeda, Thermo Fischer and Tillots.

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Honap, S., Jairath, V., Danese, S. et al. Navigating the complexities of drug development for inflammatory bowel disease. Nat Rev Drug Discov 23, 546–562 (2024). https://doi.org/10.1038/s41573-024-00953-0

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