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

IntroductionThe 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.MethodsEligible 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.ResultsA 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.ConclusionRavagalimab treatment was efficacious and safe in patients with moderate-to-severe UC in this proof-of-concept study.Graphical Abstract available for this article.ConclusionRavagalimab 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 RegistrationClinicalTrials.gov identifier, NCT03695185.