Tezepelumab meets co-primary and secondary endpoints in phase 3 eosinophilic esophagitis trial

Tezepelumab-ekko (Tezspire) met both co-primary endpoints and all key secondary endpoints in a phase 3 trial of adolescents and adults with eosinophilic esophagitis (EoE), according to top-line results announced by Amgen and AstraZeneca. The anti–thymic stromal lymphopoietin (TSLP) monoclonal antibody, already approved for severe asthma and chronic rhinosinusitis with nasal polyps, produced statistically significant and clinically meaningful improvements in esophageal histology and swallowing symptoms at week 24, with effects sustained through week 52.¹

"Despite the availability of first-line therapies or dietary interventions, many patients with eosinophilic esophagitis still experience substantial burden, including difficulty swallowing food and emotional and daily-life impacts of the disease," said Arjan Bredenoord, MD, gastroenterologist and professor at Amsterdam University Medical Center and primary investigator on the trial. "The impressive results from the CROSSING trial sustained over 52 weeks demonstrate that tezepelumab, taken every 4 weeks, could provide a new approach to treating EoE, with the potential to help more patients achieve remission and symptom improvement."

Trial design and efficacy findings for tezepelumab in EoE

CROSSING is a randomized, double-blind, placebo-controlled, multicenter, parallel-group trial that enrolled 368 patients aged 12 to 80 years with symptomatic, histologically active EoE. Participants were randomized 1:1:1 to a low or high subcutaneous dose of tezepelumab or placebo, administered every 4 weeks, while remaining on stable background therapies such as proton pump inhibitors or swallowed topical corticosteroids.²

The co-primary endpoints, assessed at week 24, were histologic remission—defined as a peak esophageal eosinophil count of 6 or fewer per high-power field—and mean change from baseline in the Dysphagia Symptom Questionnaire (DSQ), a 4-item patient-reported measure of swallowing difficulty scored from 0 to 84. Key secondary endpoints, evaluated at week 52, included histologic remission, dysphagia symptoms, endoscopic disease features (EoE-EREFS), histologic severity and extent (EoE-HSS), endoscopic response, inflammatory remission, and total endoscopic remission. The companies reported that tezepelumab separated from placebo on all of these measures, though granular efficacy figures have not yet been disclosed; full data are expected at an upcoming medical meeting. The safety profile was described as generally consistent with tezepelumab's approved indications.

Disease burden and unmet need in EoE

EoE is a chronic, progressive, epithelial-driven inflammatory disorder of the esophagus that affects more than 470,000 people in the United States, with prevalence rising roughly fivefold since 2009. Left uncontrolled, esophageal inflammation can lead to dysphagia, food impaction, and esophageal narrowing, with substantial effects on quality of life, anxiety, and school or work productivity. Standard first-line management includes dietary elimination, proton pump inhibitors, and swallowed topical corticosteroids, but nearly half of patients—including adolescents—do not achieve adequate disease control with these approaches.^3,4

TSLP inhibition as a therapeutic mechanism

Tezepelumab blocks TSLP, an epithelial-derived cytokine that initiates multiple inflammatory cascades implicated in allergic and eosinophilic disease. Unlike therapies that target downstream type 2 mediators, TSLP inhibition acts further upstream, at the airway and gut epithelium's point of contact with environmental triggers. Dupilumab, an IL-4/IL-13 pathway inhibitor, is currently the only biologic approved by the FDA for EoE, a status it has held since 2022. Tezepelumab's mechanism differs, and if these data hold up under regulatory review, it would represent a distinct therapeutic approach rather than a mechanistic follow-on.¹

References

1. Amgen. Tezspire demonstrates positive phase 3 results in eosinophilic esophagitis across both co-primary and all key secondary endpoints [press release]. Published August 27, 2026. Accessed September 14, 2026. https://www.amgen.com/newsroom/press-releases/2026/08/tezspire-demonstrates-positive-phase-3-results-in-eosinophilic-esophagitis-across-both-co-primary-and-all-key-secondary-endpoints

2. ClinicalTrials.gov. Efficacy and Safety of Tezepelumab in Patients With Eosinophilic Esophagitis (CROSSING). NCT05583227. Accessed September 14, 2026. https://clinicaltrials.gov/study/NCT05583227

3. Thel HL, Anderson C, Xue AZ, Jensen ET, Dellon ES. Prevalence and Costs of Eosinophilic Esophagitis in the United States. Clin Gastroenterol Hepatol. 2025;23(2):272-280.e8. doi:10.1016/j.cgh.2024.09.031

4. Dellon ES, Muir AB, Katzka DA, et al. ACG Clinical Guideline: Diagnosis and Management of Eosinophilic Esophagitis. Am J Gastroenterol. 2025;120(1):31-59. doi:10.14309/ajg.0000000000003194