NEJM evidence · 2025
Cendakimab in Adults and Adolescents with Eosinophilic Esophagitis.
СтатьяРандомизированное исследованиеКлиническое исследование III фазыМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Dellon Evan S, Charriez Christina M, Zhang Sandra, Falk Gary W, Oliva Salvatore, Ma Christopher, Siffledeen Jesse, Schroeder Shauna, Philpott Hamish, Vanuytsel Tim, Abe Yasuhiko, Li Kexuan, Zema Carla L, Venkatasamy Ashwini, Yeshokumar Anusha K, Oh Young S, Schoepfer Alain
Аннотация
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.).
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.).