Tezepelumab Meets Co-Primary End Points in Phase 3 CROSSING Trial in EoE

Tezepelumab, an antibody targeting thymic stromal lymphopoietin (TSLP), significantly improved histologic remission and dysphagia symptoms vs placebo in adults and adolescents with eosinophilic esophagitis (EoE) in the phase 3 CROSSING trial. The late-breaking results were presented at the American College of Gastroenterology (ACG) 2026 Annual Scientific Meeting in Nashville, Tennessee.¹

At week 24, histologic remission was achieved by 64.8% of patients receiving tezepelumab 210 mg and 68.9% receiving 420 mg, compared with 3.5% receiving placebo.¹

TSLP is an epithelial alarmin released in response to food and environmental allergens, driving downstream type 2 inflammation through IL-4, IL-5, and IL-13.¹ Tezepelumab (Tezspire) is approved by the US Food and Drug Administration for severe uncontrolled asthma and inadequately controlled chronic rhinosinusitis with nasal polyps.³

In an interview with HCPLive, Evan Dellon, MD, of the University of North Carolina School of Medicine, noted TSLP levels are elevated in EoE and variants in the TSLP gene have been linked to the disease.

CROSSING Phase 3 Trial Design and Patient Population

CROSSING randomized patients aged 12 to 80 years with symptomatic, histologically active EoE in a 1:1:1 ratio to subcutaneous tezepelumab 210 mg, tezepelumab 420 mg, or placebo every 4 weeks for 52 weeks.^1,2 Co-primary end points at week 24 were histologic remission, defined as a peak count of 6 or fewer eosinophils per high-power field at all esophageal levels, and change in Dysphagia Symptom Questionnaire (DSQ) score.¹

Of 365 treated patients, 12.3% were adolescents, and mean baseline peak eosinophil count was 90.4 per high-power field. Patients could continue stable proton pump inhibitors (42.7%), swallowed topical corticosteroids (15.1%), or elimination diets (14.8%) during the trial. Overall, 20.8% had prior esophageal dilation and 3.8% had prior dupilumab exposure.¹

Dellon said permitting background swallowed topical corticosteroids was unusual among EoE trials, allowing tezepelumab to be tested as add-on therapy.

“In this study, someone could maintain on topical steroids and use the tezepelumab as an add-on,” he said. “So that’s kind of a consideration that we all also have to think about as we think about whether and how to use this in the future.”

Tezepelumab Efficacy in EoE Through Week 52

Treatment differences in histologic remission vs placebo were 60.5 percentage points for 210 mg and 65.8 points for 420 mg (both P <.001). At week 52, histologic remission rates were 63.3% and 67.8% vs 5.4% with placebo.¹

Least-squares mean DSQ score improved by 18.80 points with 210 mg and 22.02 points with 420 mg, compared with 14.73 points with placebo. The differences vs placebo were −4.07 (P = .049) and −7.29 (P <.001), respectively.¹ Dellon said symptom benefits appeared as early as week 4 and continued to improve through week 52.

“For people in the field who do these trials, that’s always the question: whether the symptoms will improve,” said Dellon. “Here we saw great improvement with symptoms, so it looks like it’s an efficacious medicine.”

Endoscopic Reference Score (EREFS) decreased by 3.59 and 3.65 points with tezepelumab vs 0.21 points with placebo at week 24 (both P <.001). EoE Histology Scoring System grade and stage scores also improved significantly with both doses, and the investigators reported both doses met all key secondary end points at week 52.¹

Tezepelumab Safety Profile in Eosinophilic Esophagitis

Over 52 weeks, adverse events (AEs) occurred in 80.3% and 82.0% of patients receiving tezepelumab 210 mg and 420 mg, respectively, vs 77.7% with placebo. Serious AEs occurred in 3.3%, 4.9%, and 3.3%, respectively, and no deaths were reported.¹

Two serious AEs were considered possibly related to tezepelumab: an anaphylactic reaction with 210 mg and a migraine with 420 mg. The most common AEs across groups were nasopharyngitis and headache, and AEs leading to discontinuation occurred in 2% or fewer of patients in each group.¹

Dellon said tezepelumab’s position in the EoE treatment algorithm remains unclear, noting guidelines currently position biologics as step-up therapy. Detailed week 52 results are scheduled for presentation at United European Gastroenterology Week 2026.¹

Editor's note: Dellon reports relevant disclosures with AbbVie, Alfasigma, AstraZeneca, Ferring, GSK, Phathom, Regeneron Pharmaceuticals Inc., Sanofi, Shire/Takeda, Target RWE, and others.

References

1. Dellon ES, Bredenoord AJ, Rothenberg ME, et al. Efficacy and safety of tezepelumab in adults and adolescents with eosinophilic esophagitis: results from the phase 3 CROSSING study. Presented at: American College of Gastroenterology 2026 Annual Scientific Meeting; October 9-14, 2026; Nashville, TN.

2. ClinicalTrials.gov identifier: NCT05583227. Accessed October 14, 2026. https://clinicaltrials.gov/study/NCT05583227

3. Tezspire (tezepelumab-ekko). Prescribing information. US Food and Drug Administration. Accessed October 14, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761224s006lbl.pdf