Tezepelumab has met both co-primary and all key secondary endpoints in eosinophilic esophagitis, Amgen (Nasdaq: AMGN) and AstraZeneca reported on August 27, extending the anti-thymic stromal lymphopoietin (TSLP) antibody's demonstrated efficacy to a third epithelial-driven inflammatory disease after severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP).
The Phase III CROSSING trial enrolled 368 patients aged 12–80 years with symptomatic, histologically active eosinophilic esophagitis (EoE) uncontrolled on maintenance therapy, randomized 1:1:1 to low-dose tezepelumab, high-dose tezepelumab, or placebo, all administered subcutaneously every four weeks. Co-primary endpoints at week 24 were histologic remission — defined as a peak esophageal eosinophil count of six or fewer per high-power field — and mean change from baseline in the patient-reported Dysphagia Symptom Questionnaire (DSQ) score. Both were met with statistically significant and clinically meaningful improvements versus placebo, the companies said, and those improvements were sustained through week 52. All key secondary endpoints, including endoscopic disease features, histologic severity, and total endoscopic remission at week 52, were also met. Specific numerical results have not been disclosed; full data will be presented at an upcoming medical meeting.
The safety profile was described as generally consistent with tezepelumab's approved indications. Tezepelumab (Tezspire) is currently approved for severe asthma in the US, EU, China, Japan, and more than 70 countries, and received FDA approval for CRSwNP in October 2025 based on the Phase III WAYPOINT trial, which showed a 98% reduction in surgery need and 88% reduction in systemic corticosteroid use versus placebo.
Tezepelumab blocks TSLP, an epithelial cytokine that sits upstream of multiple inflammatory cascades. In EoE, TSLP is preferentially secreted by terminally differentiated esophageal epithelial cells and is believed to initiate the eosinophilic inflammation that drives dysphagia, food impaction, and esophageal remodeling. By acting at this upstream checkpoint rather than targeting downstream mediators such as IL-5 or IL-13, tezepelumab intervenes earlier in the inflammatory cascade rather than targeting individual effector pathways — a distinction the companies have consistently emphasized across indications.