Cendakimab in Adults and Adolescents with Eosinophilic Esophagitis.

Abstract

Background: Eosinophilic esophagitis (EoE) is a chronic type 2 inflammatory esophageal disease driven by interleukin 13 (IL-13). Cendakimab, a high-affinity monoclonal antibody, binds IL-13, blocking interaction with receptors IL-13 receptor alpha 1 and IL-13 receptor alpha 2.

Methods: In this phase 3 trial, we randomly assigned patients with EoE 12 to 75 years of age to cendakimab 360 mg once weekly for 48 weeks (QW/QW), cendakimab 360 mg once weekly (QW) for 24 weeks, then 360 mg every other week for weeks 24 to 48 (QW/Q2W), or placebo for 48 weeks. Coprimary end points at week 24 were change from baseline in dysphagia days, measured by a validated patient-reported modified Daily Symptom Diary, and histologic response (peak esophageal eosinophil count ≤6 per high-power field). Secondary end points included endoscopic features and safety. Cendakimab QW/QW and QW/Q2W regimens were assessed as a single treatment group in the analyses from week 0 to week 24 (cendakimab QW) and as separate treatment groups versus placebo in the analyses from weeks 24 to 48.

Results: Among 430 patients randomly assigned to cendakimab (QW/QW, n=143; QW/Q2W, n=143) or placebo (n=144), reduction from baseline in dysphagia days at week 24 was significantly greater with cendakimab QW versus placebo (least-squares mean change [standard error], -6.1 [0.3] vs. -4.2 [0.4] days; P<0.001). Histologic response at week 24 was achieved in 28.6% of patients with cendakimab QW versus 2.2% with placebo (P<0.001). Cendakimab improved endoscopic severity from baseline to week 24, compared with placebo (least-squares mean change [standard error] -5.2 [0.24] points vs. -1.2 [0.34] points). Efficacy was maintained at week 48. Adverse events occurred in 83.8%, QW/QW, and 84.6%, QW/Q2W, of patients with cendakimab and 73.4% with placebo through week 48.

Conclusions: Cendakimab demonstrated statistically significant improvements in symptoms, histologic response, and endoscopic features of EoE versus placebo; the adverse-event and side-effect profile was not dose limiting. (Funded by Bristol Myers Squibb; ClinicalTrials.gov number, NCT04753697.).