Cendakimab meets primary endpoints in eosinophilic oesophagitis

Cendakimab outperformed placebo in participants with eosinophilic oesophagitis (EoE) across various efficacy endpoints in a phase 3 study. These results were consistent in the sub-population of steroid-refractory participants.

“EoE is a chronic, progressive, immune-mediated inflammatory disease, characterised by oesophageal inflammation with eosinophilic infiltration,” said Prof. Alain Schoepfer (University of Lausanne, Switzerland) [1]. “This process is mainly driven by the type 2 inflammatory cytokine IL-13.” In a previous phase 2 study, the IL-13 inhibitor cendakimab was associated with improved symptoms and reduced oesophageal eosinophil counts in participants with EoE [2].

A randomised-controlled, phase 3 trial (NCT04753697) tested cendakimab against a placebo in a large population of participants with EoE (n=430) aged between 12 and 75 years [1]. Participants were allocated to a weekly dose of cendakimab 360 mg subcutaneously (n=286) or a placebo (n=144). The co-primary endpoints were the mean change in dysphagia days from baseline to week 24, assessed using the modified daily symptom diary, and the proportion of participants with a histologic response (peak eosinophil count ≤6/high-power field) at week 24.

For the first primary endpoint, the least square mean changes were -6.1 days for the intervention arm and -4.2 days for the placebo arm (difference -1.9; 95% CI -3.0 to -0.8; P=0.0005). The other primary endpoint also significantly favoured the cendakimab arm over the placebo arm (28.6% vs 2.2%; difference 26.4%; 95% CI 20.6–32.2; P<0.0001; see Figure). “Cendakimab was superior to placebo in terms of endoscopic response and other key secondary endpoints as well,” commented Dr Schoepfer. “Furthermore, the findings were consistent in steroid-refractory participants.”

Figure: Co-primary endpoints at week 24 of the phase 3 trial in participants with EoE [2]



CEN, cendakimab; EoE, eosinophilic oesophagitis; hpf, high-power field; LSM, least square mean; PEC, peak eosinophil count; PBP, placebo; QW, once a week.

The adverse event (AE) rates were fairly comparable between groups, with any AEs occurring in 76.4% of the participants on cendakimab and in 68.5% of those on placebo. Serious AEs were rare, with rates of 1.8% and 2.8% in the active and control arms, respectively. Injection site reactions (16.9%), COVID-19 (14.1%), and headache (9.2%) were the most common AEs in the cendakimab arm.

“In this large phase 3 study, cendakimab met the co-primary endpoints, demonstrating statistically significant improvements in symptoms and reductions in oesophageal eosinophils in participants with EoE through 24 weeks,” summarised Prof. Schoepfer.

1. 
   
   1. Schoepfer A, et al. Cendakimab efficacy and safety in adult and adolescent patients with eosinophilic esophagitis: 24-week results from the randomized, placebo-controlled, phase 3 study. LB11, UEG Week 2024, 12–15 October, Vienna, Austria.
   2. Hirano I, et al. Gastroenterology. 2019;156:592-603.e10.

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Posted on 28 November 202428 November 2024