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The investigational monoclonal antibody cendakimab significantly improved symptoms and reduced esophageal eosinophils in patients with eosinophilic esophagitis at 24 weeks, a randomized phase III trial showed.

Of the 430 patients, those receiving cendakimab had a least-squares mean change from baseline to week 24 of -6.1 dysphagia days compared with -4.2 dysphagia days in the placebo group (P=0.0005), reported Evan S. Dellon, MD, MPH, of the University of North Carolina at Chapel Hill, at the American College of Gastroenterology annual meeting in Philadelphia.

In addition, 28.6% of patients receiving cendakimab had an eosinophil histologic response, defined as a peak eosinophil count (PEC) of ≤6 per high-powered field (hpf), compared with 2.2% of placebo patients (P<0.0001).

Responses seen at 6 months continued through 12 months, and cendakimab, which targets interleukin (IL)-13 at both its receptors, was well tolerated, with no drug-related serious adverse events.

Amrit K. Kamboj, MD, of Cedars-Sinai Medical Center in Los Angeles, who was not involved with the study, told MedPage Today that the results were promising.

"A striking finding was that this positive response was seen in patients with EoE [eosinophilic esophagitis] despite all having lack of complete response to proton pump inhibitors [PPIs], and two-thirds (66%) being inadequate responders and/or intolerant of steroids, both commonly utilized treatments for EoE," said Kamboj.

"At present, there are limited treatment options for patients with EoE, including PPIs, topical corticosteroids, dupilumab [Dupixent], and various elimination diets," he explained. "The results from this multicenter, multinational study suggest that cendakimab may also be an effective treatment for EoE, especially in those who have failed other therapies such as PPIs."

enrolled 430 patients with active eosinophilic esophagitis and no response to at least 8 weeks of treatment with PPIs. Across the groups, mean age was 35-36 (6-12% were adolescents), 63-77% were men, and 42-50% were taking PPIs. Mean number of years since diagnosis was 5.2 to 6.3 years.

Of the participants, 143 received 360 mg of subcutaneous cendakimab once weekly and 143 started at 360 mg once weekly and then switched at 24 weeks to once every other week, while 144 patients received once-weekly subcutaneous placebo. Nearly all patients remained in the trial at week 24, except two receiving cendakimab and one receiving placebo.

Only 90 of the patients receiving placebo opted to continue to 48 weeks, compared with 114 receiving once-weekly cendakimab and 117 receiving cendakimab every other week.

For the secondary endpoints at 48 weeks, those receiving placebo had 2.7 fewer dysphagia days compared with 4.9 fewer days with once-weekly cendakimab (P=0.0006) and 5.2 fewer days with cendakimab every other week (P=0.0002).

Based on the Eosinophilic Esophagitis Endoscopic Reference Score measuring endoscopic response, the least-squares mean change from baseline to 48 weeks was -0.7 points in the placebo group compared with -4.2 points in the once-weekly cendakimab group and -3.8 points in the every other week group (P<0.0001 for both).

Secondary endpoints for eosinophil histologic response included assessment of PEC of ≤6 and <15 per hpf. A PEC of ≤6/hpf at 48 weeks occurred in 2.1% of placebo patients compared with 20.6% in the weekly cendakimab group (P<0.0001) and 19.2% in the every other week group (P<0.0001). A PEC of <15/hpf occurred in 2.2%, 27.9%, and 30.1%, respectively (P<0.0001 for both).

The change in the composite score of the modified Daily Symptom Diary was a least-squares mean of 5.2 fewer points in the placebo group compared with 9.6 fewer points in the once-weekly cendakimab group (P=0.002) and 10.4 fewer points in the every other week group (P=0.0003).

Based on the eosinophilic esophagitis histology scoring system, placebo patients had a mean grade score change of -0.7 points compared with -18.9 points in the once-weekly cendakimab group and -20.0 points in the every other week group (P<0.0001 for both). The mean changes in stage score were -1.2, -22.0, and -24.6 points, respectively (P<0.0001 for both).

Total adverse events occurred at similar rates across all groups; 33.5% of patients in the cendakimab group experienced adverse events related to the study drug compared with 21% of the placebo group. Though 5.6% of placebo patients and 2.8% of cendakimab patients experienced any serious adverse event, none were suspected to result from the study drug. The most common adverse events, occurring in at least 10% of patients, were COVID-19, injection-site reactions, nasopharyngitis, upper respiratory tract infection, and headache.

Kamboj said it will be important to learn more about longer-term outcomes with cendakimab, but noted that fewer than 3% of patients discontinued the drug due to adverse events.

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