Promising phase II biologics for future Crohn’s disease therapy

ABSTRACT

Introduction

Although the physician’s therapeutic arsenal of Crohn’s Disease (CD) is rapidly expanded over the next 25 years, a significant proportion of patients remain non-responders, or develop a loss of response or intolerance to current therapies, indicating a need for new therapeutic strategies in CD.

Areas covered

This review examines the efficacy and safety data from phase II clinical trials on biologics, performed in patients with moderate-to-severe CD. A PubMed database literature review was conducted for relevant articles published from 2017 to 2022. Ongoing clinical phase II trials were retrieved from ClinicalTrials.gov database or abstracts from major congresses. Future perspectives for the treatment of CD patients with these new molecules were also discussed.

Expert opinion

Among the most promising biologics are interleukin (IL)-23p19 inhibitors (guselkumab, mirikizumab, and brazikumab), IL-6 inhibitors, and anti-adhesion molecules (ontamalimab). Furthermore, multiple biologics with different mechanisms of action are in clinical development for moderate-to-severe CD including molecules with anti-fibrotic mechanism of action (anti-TL1A, anti-IL-36 receptor). In addition to efficacy, some of them provide reassuring safety profiles. Phase III trials need to confirm these results, especially on their long-term safety issues.

KEYWORDS:

• biologics
• Crohn’s disease
• inflammatory bowel diseases
• Phase II
• randomized trials

Article highlights

• Several biologic therapies are currently in phase II development to address the therapeutic unmet need in CD.

• Selective IL-23p19 inhibitors (mirikizumab, guselkumab, brazikumab) showed promising results in phase II clinical trials regarding clinical and endoscopic outcomes (for mirikizumab) with a reassuring safety profile.

• IL-6 inhibitors demonstrated encouraging efficacy data, however, some safety concerns with PF-04236921 were reported.

• Ontamalimab, is a human monoclonal antibody targeting MAdCAM-1. In CD, ontamalimab is more effective than placebo but differences were not significant in bio-exposed CD patients.

• Biologics with new mechanisms of action (anti-fibrotic drugs: anti-TL1A, anti-IL-36 receptor) or with oral administration (V565) are currently in an early phase of development in CD.

Declaration of interest

P Wils declares lecture fees from AbbVie, Ferring, Biogen, Janssen.

S Danese reports consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, EliLilly, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial,Vifor They also report lecture fees from Abbvie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer, Takeda.

L Peyrin-Biroulet declares consulting fees from AbbVie, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HAC-Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Sanofi, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax. They also declare grants from Takeda, Fresenius Kabi, Celltrion and declare lecture fees from Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Lilly, Gilead, Viatris, Medac.

Authors’ Contributions

P Wils wrote the article. P Wils, S Danese and L Peyrin-Biroulet critically revised the manuscript. The manuscript was approved by all authors.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.