P0842 Paediatric Inflammatory Bowel Diseases: novel agents on the therapeutic horizon
Authors: Gupte D , Suthar N R , MacDonald J K , Colman R J , Feagan B , Hanzel J , Ma C , Jairath V , Crowley E 
Published: January 2025

Abstract

Background
The therapeutic landscape for inflammatory bowel disease (IBD) has advanced considerably over the past two decades with the development of monoclonal antibodies and advanced small molecules. However, only one advanced therapy class is approved for children with IBD. Long delays exist following adult approval, with a median delay of over seven years to paediatric approval (Figure 1).1 With the recent circulation of draft guidance for industry on drug development in paediatric IBD (pIBD) by the US Food and Drug Administration (FDA),2 an opportunity exists to improve clinical trial processes for drug approval in pIBD. The aim of this study is to summarize the landscape of pIBD clinical trials through a review of trial registries.

Methods
We conducted a cross-sectional review of publicly accessible data from Clinicaltrials.gov and ClinicalTrialsRegister.eu to identify investigational therapeutic agents as well as approved therapeutic agents for the treatment of pIBD. All interventional pIBD studies (&lt;18 years and/or included a paediatric population) listed from the database’s inception to May 13, 2024, were considered for inclusion.

Results
A total of 3,493 records were identified from Clinicaltrials.gov (2,758) and ClinicalTrialsRegister.eu (735). One-hundred and sixteen completed trials were included in the review. Of those completed trials, 34 studies focused on biologic agents (29%). Novel small molecule agents (spingosine-1-phosphate agonists and Janus kinase inhibitors) were examined in 7 studies (6%). A further 118 IBD trials are actively recruiting paediatric patients. Sixty-five studies are randomised controlled trials and 53 are open-label studies. With regards to biologic agents, 17 trials are exploring the use of approved biologic agents in children and 34 trials are focusing on novel biologic agents. These include etrolizumab, golimumab, guselkumab, mirikizumab, risankizumab, ustekinumab, and vedolizumab. Sixteen trials are recruiting, examining small molecule therapies in pediatrics, to include upadacitinib, tofacitinib, etrasimod, and ozanimod.

Conclusion
Efforts to hasten the approvals of novel agents in pIBD is paramount to ensure timely access to effective medications. Whilst there is increasing trial activity in the pIBD landscape, approval by regulatory bodies continue to pose barriers. Consideration for novel trial designs and collaboration between research networks could reduce the delay in paediatric marketing approvals. Continued engagement with regulatory bodies and the international pIBD community offers a critical opportunity to advance drug approvals in children with IBD.

References
1.Crowley E, Ma C, Andic M, Feagan BG, Griffiths AM, Jairath V. Impact of Drug Approval Pathways for Paediatric Inflammatory Bowel Disease. J Crohns Colitis. 2022;16(2):331-5
2.U.S Food and Drug Administration. Pediatric Inflammatory Bowel Disease: Developing Drugs for Treatment. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/pediatric-inflammatory-bowel-disease-developing-drugs-treatment
3.Created in BioRender. Suthar, N. (2024) BioRender.com/l43j981