AZ, Amgen: TSLP is an important mediator of inflammation in severe asthma

AstraZeneca and Amgen on Thursday published results from the PATHWAY Phase IIb trial of tezepelumab that showed a significant reduction in the annual asthma exacerbation rate compared with placebo in patients with severe, uncontrolled asthma. The trial results were published in the New England Journal of Medicine. The PATHWAY trial achieved its primary efficacy endpoint, showing annual asthma exacerbation rate reductions.

Tezepelumab also demonstrated improvements in lung function at all doses and in asthma control at the two higher doses.

Dr Jonathan Corren, the Principal Investigator of the PATHWAY trial, said that the results strongly confirm that TSLP is an important mediator of inflammation in severe asthma. He said that due to its activity early in the inflammatory cascade, tezepelumab may be suitable for patients with both T2 and non-T2 driven asthma, including those ineligible for current biologic therapies which only target the T2 pathway.

Bahija Jallal, Head of MedImmune, said: “In asthma patients, TSLP functions as an upstream epithelial ‘master-switch’ right at the start of the inflammation cascade. By binding to TSLP, tezepelumab impacts multiple downstream inflammatory pathways associated with asthma, as shown by striking reductions in the level of multiple biomarkers in the PATHWAY trial, including blood eosinophils, IgE and FeNO. This broad biomarker response is unprecedented among respiratory biologics and reflects our commitment to leading respiratory science for unmet medical needs.“

TSLP is an epithelial cytokine produced in response to pro-inflammatory stimuli such as allergens, viruses and other pathogens in the lung. It drives the release of downstream T2 cytokines including IL-4, IL-5 and IL-13, leading to inflammation and asthma symptoms. TSLP also activates many types of cells involved in non T2 driven inflammation. Therefore, the early, upstream activity of TSLP in the inflammation cascade has been identified as a potential target across a broad asthma population.