Topline results from a phase II clinical trial indicate that itolizumab, an investigational anti-CD6 monoclonal antibody, may offer a potential new treatment approach for patients with moderate to severe ulcerative colitis.¹ The therapy is designed to target the CD6-ALCAM pathway, a mechanism implicated in gastrointestinal inflammation.² In these initial results, released in a press release by the study’s co-sponsors, Equillium Inc. and Biocon Ltd, itolizumab demonstrated clinical remission rates comparable to adalimumab, reinforcing its potential role in the evolving treatment landscape for inflammatory bowel disease.¹
The randomized, double-blind study enrolled 90 patients who were biologic-naïve with moderate to severe ulcerative colitis, assigning them 1:1:1 to receive either itolizumab (140 mg), adalimumab, or placebo every two weeks for 12 weeks.¹ The study’s primary endpoint was clinical remission, defined using the Total Mayo Score, with secondary endpoints assessing clinical response and endoscopic remission.
Despite a higher proportion of severe disease cases in the itolizumab arm, the therapy achieved clinical remission in 23.3% of patients, compared to 20.0% for adalimumab and 10.0% for placebo.¹ Clinical response rates were also encouraging, with 63.3% of patients receiving itolizumab responding, compared to a 60.0% response rate in those receiving adalimumab and a 46.7% response rate in those receiving placebo. Endoscopic remission was reported in 16.7% of both the itolizumab and adalimumab groups, while only 6.7% of patients treated with placebo reached this benchmark. The drug was also reported to be well tolerated, with no significant safety concerns emerging during the study.
The CD6-ALCAM pathway is increasingly recognized for its role in modulating T cell activity and driving inflammation in autoimmune diseases such as ulcerative colitis and Crohn’s disease.³ Unlike TNF inhibitors, which broadly suppress inflammatory signaling, itolizumab is thought to selectively downregulate pathogenic T effector cells while preserving regulatory T cell function, an approach that could potentially offer improved disease control while maintaining immune balance.⁴,⁵
Dr. Stephen Connelly, Chief Scientific Officer at Equillium, emphasized the significance of these findings, particularly in light of itolizumab’s broader development program. “While the phase III EQUATOR study is primarily evaluating the therapy in acute graft-versus-host disease, where lower gastrointestinal inflammation is a major complication, the ulcerative colitis data strengthen the case for targeting CD6-ALCAM as a therapeutic strategy”.¹
Further content in digestive diseases.
References
Equillium Inc. Equillium Announces Positive Data from Phase 2 Study Evaluating Itolizumab in Patients with Moderate to Severe Ulcerative Colitis [Press release]. Available at: (accessed 24 Feb 2025).
Marrocco V, Ampudia J, Ng C, et al. Blocking the CD6-ALCAM Pathway Prevents Transendothelial Migration of Pathogenic Effector T Cells. Blood. 2022;140(Suppl 1):12657-12658.
Ma C, Wu W, Lin R, et al. Critical Role of CD6highCD4+ T Cells in Driving Th1/Th17 Cell Immune Responses and Mucosal Inflammation in IBD. J Crohns Colitis. 2019 Mar 30;13(4):510-524. doi: 10.1093/ecco-jcc/jjy179.
Rajput A, Ware CF. TNF Inhibitor. In: Encyclopedia of Cell Biology. 2016. Available at: https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/tnf-inhibitor (accessed 24 Feb 2025).
Rambaldi B, Kim HT, Arihara Y, et al. Phenotypic and functional characterization of the CD6-ALCAM T-cell co-stimulatory pathway after allogeneic cell transplantation. Haematologica. 2022 Nov 1;107(11):2617-2629. doi: 10.3324/haematol.2021.280444.
Editor: Gina Furnival, Senior Editorial Director
Support: No funding was received in the publication of this short article.
Cite: Novel anti-CD6 monoclonal antibody, itolizumab, showcases proof of concept in ulcerative colitis. touchIMMUNOLOGY February 26, 2025.
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