Tezepelumab-ekko (Tezspire) Meets Co-Primary Endpoints in Phase 3 Eosinophilic Esophagitis Trial

Amgen and AstraZeneca announced positive topline results from the phase 3 CROSSING trial of tezepelumab-ekko (Tezspire) in patients with eosinophilic esophagitis (EoE), meeting both co-primary endpoints and all key secondary endpoints, the companies said August 27, 2026.¹ Improvements in histologic remission and dysphagia frequency and severity were statistically significant and clinically meaningful at week 24 and sustained through week 52, with a safety profile generally consistent with tezepelumab's approved indications.¹

"We're pleased that Tezspire showed efficacy in a third epithelial-driven inflammatory condition, eosinophilic esophagitis," said Jay Bradner, MD, executive vice president of research and development, artificial intelligence and data at Amgen, in a company press release.¹ "In this [p]hase 3 trial, Tezspire improved both the underlying inflammation and the swallowing difficulties that can make eosinophilic esophagitis so disruptive for patients. That combination is important for patients and builds confidence in Tezspire as a potential new treatment for people struggling with EoE."

What did the CROSSING trial show?

CROSSING (NCT05583227) is a randomized, double-blind, placebo-controlled phase 3 trial that enrolled 368 patients ages 12 to 80 with symptomatic, histologically active EoE, randomized 1:1:1 to a low or high dose of tezepelumab or placebo administered subcutaneously every 4 weeks.² The co-primary endpoints 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 patient-reported Dysphagia Symptom Questionnaire (DSQ), which scores dysphagia severity from 0 to 84.¹

Key secondary endpoints assessed histologic remission and dysphagia symptoms at week 52, along with endoscopic and histologic disease measures at weeks 24 and 52.¹ Patients were allowed to remain on stable background EoE medications, including proton pump inhibitors and swallowed topical corticosteroids, throughout the trial.

Why is a new treatment option needed for EoE?

EoE is a chronic, progressive inflammatory disorder of the esophagus affecting more than 470,000 people in the United States, with prevalence increasing 5-fold since 2009.³ Esophageal inflammation from EoE can cause dysphagia, food impaction, and esophageal narrowing, and nearly half of patients do not achieve adequate control with first-line treatments such as dietary restriction, swallowed topical corticosteroids, and proton pump inhibitors.¹

How does tezepelumab work, and what does it mean for the drug's broader development?

Tezepelumab is a first-in-class human monoclonal antibody (mAb) that targets and blocks thymic stromal lymphopoietin (TSLP), an epithelial cytokine that initiates inflammatory cascades across multiple epithelial-driven diseases. Tezepelumab is already approved in the US for severe asthma and inadequately controlled chronic rhinosinusitis with nasal polyps and is approved for severe asthma in more than 70 countries. The mAb is also in development for chronic obstructive pulmonary disease. Amgen and AstraZeneca said full CROSSING results will be shared with regulatory authorities and the scientific community at an upcoming medical meeting.¹

What did the trial's principal investigator say?

"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, PhD, gastroenterologist and professor at Amsterdam University Medical Center and primary investigator on the trial, in the release.¹ "The impressive results from the CROSSING trial sustained over 52 weeks demonstrate that tezepelumab, taken every four weeks, could provide a new approach to treating EoE, with the potential to help more patients achieve remission and symptom improvement."

What are the limitations?

These are topline results, and full data have not yet been presented at a medical meeting or published in a peer-reviewed journal. Tezepelumab is not yet approved for EoE, and regulatory filings for this indication have not been announced.

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 August 27, 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. Updated July 30, 2026. Accessed August 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