Efficacy and Safety of Ravagalimab in Patients with Moderate-to-Severe Ulcerative Colitis: Data from a Phase 2a Trial

INTRODUCTION: The monoclonal antibody ravagalimab is a potent antagonist to cluster of differentiation 40 (CD40), which is elevated in inflammatory diseases such as ulcerative colitis (UC). This phase 2a, open-label trial evaluated the efficacy and safety of ravagalimab as induction and maintenance treatment in patients with moderate-to-severe UC and who had inadequate response, loss of response, or intolerance to prior therapy. METHODS: Eligible adult patients with an adapted Mayo Score ≥ 5 points and an endoscopic subscore ≥ 2 received ravagalimab 600 mg intravenously at baseline, then 300 mg subcutaneously every 2 weeks from weeks 2 through 10. Patients with a clinical response at week 12 continued into the maintenance period (ravagalimab 300 mg subcutaneously every 2 weeks through week 102). The study was terminated early upon achieving the trial objectives at completion of the induction period. RESULTS: A total of 42 patients were enrolled and received at least one dose of ravagalimab. At baseline, over 80% of patients had severe endoscopic disease and failed/were intolerant to multiple prior biological/Janus kinase (JAK) therapies. Endoscopic improvement (Mayo endoscopic subscore of ≤ 1 without friability by independent central review) at week 8, the primary efficacy endpoint, was achieved in 18% of ravagalimab-treated patients. Ravagalimab also led to clinical remission per adapted Mayo Score (stool frequency score ≤ 1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤ 1 without friability) and clinical response per adapted Mayo Score (a decrease of ≥ 30% and ≥ 2 points from baseline and a decrease in rectal bleeding score of ≥ 1 or an absolute rectal bleeding score of ≤ 1) at week 8 in 9.5% and 40.2% of patients, respectively. In addition, gut biopsy analyses demonstrated target engagement, and pharmacodynamic modulation of a CD40-inducible gene (ICAM1) and CD40-dependent plasma cells. Ravagalimab was generally safe and well tolerated. CONCLUSION: Ravagalimab treatment was efficacious and safe in patients with moderate-to-severe UC in this proof-of-concept study. Graphical Abstract available for this article. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03695185.