AstraZeneca and Amgen’s Tezspire (tezepelumab) has demonstrated statistically significant and clinically meaningful improvements in patients with symptomatic, uncontrolled eosinophilic esophagitis (EoE), according to full results from the positive Phase III CROSSING trial.

 

The trial met both co-primary endpoints at week 24, showing significant improvements in histologic remission and the frequency and severity of dysphagia, or difficulty swallowing, in adolescent and adult patients compared with placebo. The benefits were observed despite patients continuing their stable background medications, with efficacy sustained through week 52 across key secondary endpoints.

 

Tezspire, administered as a subcutaneous injection every four weeks, achieved histologic remission at week 24 in 64.8% of patients receiving the 210mg dose and 68.9% of those receiving the 420mg dose, compared with just 3.5% of patients on placebo.

 

The treatment also improved swallowing symptoms, as measured by the patient-reported Dysphagia Symptom Questionnaire (DSQ). At week 24, DSQ scores fell by 18.8 points with the 210mg dose and 22.0 points with the 420mg dose, compared with a 14.7-point reduction with placebo. The results were statistically significant for both doses.

 

The benefits persisted through week 52. Histologic remission was achieved by 67.8% of patients receiving the 210mg dose and 63.3% receiving the 420mg dose, compared with 5.4% on placebo.

 

Swallowing symptoms also continued to improve, with average DSQ score reductions from baseline of 22.1 points for the 210mg dose and 24.0 points for the 420mg dose, compared with 13.2 points for placebo. 

 

Tezspire also produced statistically significant improvements in endoscopic features and disease severity at weeks 24 and 52, as measured by the EoE Endoscopic Reference Score (EREFS).

 

By week 52, total endoscopic remission — defined as the absence of visible EoE features — was achieved by 34.4% of patients receiving the 210mg dose and 29.5% receiving the 420mg dose, compared with 4.1% on placebo.

 

Together, the findings demonstrate improvements across three key measures of EoE: histologic remission, dysphagia symptoms and endoscopic outcomes.

 

EoE is a chronic inflammatory disease of the oesophagus that can cause difficulty swallowing, food impaction and narrowing of the oesophagus. The risk of food moving slowly or becoming stuck can make everyday meals difficult and stressful.

 

Arjan Bredenoord, international coordinating investigator in the CROSSING trial, said: “The CROSSING trial results are compelling because they show consistent, lasting improvements across three key measures of eosinophilic esophagitis — histologic remission, frequency and severity of dysphagia and endoscopic remission — sustained through 52 weeks. Importantly, these meaningful results were seen even in patients who were allowed to remain on their stable background therapy."

 

Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “The exciting results from the CROSSING trial further support the broad potential of Tezspire and its unique mode of action targeting TSLP at the top of the inflammatory cascade. These data build on the strong body of evidence for Tezspire and support its potential to transform outcomes for patients across a range of epithelial-driven inflammatory diseases. 

 

"We look forward to sharing the CROSSING data with regulatory authorities in order to bring Tezspire to patients living with eosinophilic esophagitis as quickly as possible.”