Efficacy and Safety of the Anti-Mucosal Addressin Cell Adhesion Molecule-1 Antibody Ontamalimab in Patients with Moderate-to-Severe Ulcerative Colitis or Crohn’s Disease
Séverine Vermeire, Silvio Danese, William J Sandborn, Stefan Schreiber, Stephen Hanauer, Geert D’Haens, Peter Nagy, Manoj Thakur, Caleb Bliss, Fabio Cataldi, Martina Goetsch, Kenneth J Gorelick, Walter Reinisch- Gastroenterology
- General Medicine
Abstract
Background and Aims
Ontamalimab is a fully human immunoglobulin G2 monoclonal antibody against mucosal addressin cell adhesion molecule-1 developed as treatment for inflammatory bowel disease.
Methods
Six phase 3, multicentre, randomised, double-blind, placebo-controlled clinical trials compared efficacy and safety of ontamalimab [25 mg and 75 mg once every 4 weeks] with placebo in patients with moderate-to-severe ulcerative colitis or Crohn’s disease [two induction studies and one re-randomised maintenance study per condition]. This clinical trial programme was discontinued in 2020 for reasons unrelated to drug safety/efficacy; Crohn’s disease studies are described in the supplementary materials.
Results
The induction [12-week] and maintenance [52-week] studies included 659 and 366 randomised patients, respectively. More patients who received ontamalimab induction than placebo achieved the primary endpoint of clinical remission at week 12 [25 mg, 18.5% vs 15.8% (p = 0.617), 27.0% vs 12.5% (p = 0.027); 75 mg, 29.8% vs 15.8% (p = 0.018), 29.5% vs 12.5% (p = 0.014)]; significantly more patients who received ontamalimab maintenance therapy than placebo achieved week 52 clinical remission [25 mg, 53.5% vs 8.2%, p < 0.001; 75 mg, 40.2% vs 12.8%, p < 0.001]. Endoscopic improvement was generally significantly different vs placebo [induction: 25 mg, 27.8% vs 21.1 (p = 0.253), 35.1% vs 12.5% (p = 0.001); 75 mg, 41.1% vs 21.1 (p = 0.002), 33.9% vs 12.5% (p = 0.003); maintenance: 25 mg, 56.3% vs 9.6% (p < 0.001); 75 mg, 48.8% vs 15.1% (p < 0.001)]. Adverse event rates were similar between ontamalimab and placebo groups.
Conclusions
Ontamalimab 75 mg was effective with no safety concerns as induction and maintenance therapy for patients with moderate-to-severe ulcerative colitis.