AstraZeneca and Amgen have reported positive Phase III clinical trial results for Tezspire (tezepelumab), a therapeutic they hope to expand into a third indication: eosinophilic oesophagitis (EoE).
The Phase III CROSSING trial evaluated Tezspire in adults and adolescents with symptomatic, uncontrolled EoE.
Tezspire is a monoclonal antibody that targets thymic stromal lymphopoietin (TSLP), a signalling protein released by epithelial cells that triggers inflammatory pathways.
It is already approved for severe asthma and chronic rhinosinusitis with nasal polyps in certain markets.
The companies tested two doses, 210 mg and 420 mg, administered by subcutaneous injection every four weeks.
Key results
Results were assessed at 24 and 52 weeks.
At week 52, 63.3–67.8% of patients receiving Tezspire achieved histologic remission, compared with 5.4% of those receiving placebo, indicating reduced tissue inflammation.
Tezspire also reduced the severity and frequency of dysphagia symptoms (difficulty swallowing).
At week 24, the Dysphagia Symptom Questionnaire (DSQ) score fell by 18.8 points with the 210 mg dose and 22.0 points with the 420 mg dose, compared with a 14.7-point reduction with placebo.
Additionally, 29.5-34.4% of patients achieved endoscopic remission at week 52, compared with 4.1% of those receiving placebo.
The companies reported that improvements were sustained through week 52, with benefits across key measures of inflammation, symptoms and endoscopic disease activity.
Commercial implications
For Amgen and AstraZeneca, the results have three main commercial and strategic implications.
Tezspire is already approved for severe asthma and chronic rhinosinusitis in certain markets; thus, EoE would be a third indication if approved.
This could expand the number of patients eligible for treatment and increase the drug's commercial potential.
The results also demonstrate the potential of a shared biological target — as TSLP is involved in multiple inflammatory processes, positive results in EoE suggest that blocking this signalling molecule may be useful beyond the diseases for which Tezspire is already approved.
The pair also said they are studying it in chronic obstructive pulmonary disease (COPD) in a separate clinical development programme.
Finally, Amgen and AstraZeneca can build on Tezspire's established clinical and manufacturing infrastructure to develop a new indication for the therapeutic, instead of developing the molecule entirely from scratch.
However, the companies did not announce any specific manufacturing changes linked to the EoE programme.
“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," said Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca.
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.
“A new treatment approach is needed for people living with eosinophilic esophagitis, half of whom continue to experience uncontrolled symptoms despite standard treatment," added Dr Jay Bradner, Executive Vice President of Research and Development, Artificial Intelligence and Data at Amgen.
"We’re pleased with the statistically significant and clinically meaningful, sustained improvements seen in CROSSING."
As we continue to study TEZSPIRE across epithelial-driven inflammatory diseases, our focus remains on translating the science behind TSLP inhibition into meaningful outcomes for patients.
What happens next?
The companies said the CROSSING results will be shared with regulatory authorities. Further regulatory review will be needed before Tezspire can be used to treat EoE, as the indication has not yet been approved.
If authorised, the therapy could offer another treatment option for people whose symptoms and inflammation remain inadequately controlled by existing approaches.
