AstraZeneca and Amgen have announce 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. Tezepelumab is a first-in-class anti-TSLP monoclonal antibody being developed by MedImmune, AstraZeneca’s global biologics research and development arm, in collaboration with Amgen.

The trial results are published in the New England Journal of Medicine on 7 September and will be followed by an oral presentation on 12 September at the ERS International Congress 2017 in Milan.

The PATHWAY trial achieved its primary efficacy endpoint, showing annual asthma exacerbation rate reductions of 61%, 71% and 66% in the tezepelumab arms receiving either 70mg or 210mg every four weeks or 280mg every two weeks, respectively (p<0.001 for all comparisons to placebo). In the trial, tezepelumab was given as an add-on therapy to patients with a history of asthma exacerbations and uncontrolled asthma despite receiving inhaled corticosteroids/long-acting beta-agonists with or without oral corticosteroids and additional asthma controllers.

Significant and clinically-meaningful reductions in the exacerbation rate were observed independent of baseline blood eosinophil count or other type 2 (T2) inflammatory biomarkers. Tezepelumab also demonstrated improvements in lung function at all doses and in asthma control at the two higher doses (p<0.05 for all comparisons to placebo). The incidence of adverse events was similar between the tezepelumab and placebo groups. The most common adverse events (=5%) in tezepelumab-treated patients were asthma, nasopharyngitis, headaches and bronchitis.

Dr Jonathan Corren, David Geffen School of Medicine, UCLA and Principal Investigator of the PATHWAY trial, said: “These efficacy results strongly confirm that TSLP is an important mediator of inflammation in severe asthma. 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, Executive Vice President, 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.