Amgen and AstraZeneca's First-in-Class Anti-TSLP Antibody Tezepelumab Receives FDA Priority Review for Severe Asthma

On July 8, 2021, Amgen and AstraZeneca jointly announced that the U.S. FDA has accepted the Biologics License Application (BLA) for tezepelumab, a monoclonal antibody therapy targeting thymic stromal lymphopoietin (TSLP) co-developed by the two companies for the treatment of asthma, and granted it Priority Review designation. The PDUFA date is scheduled for the first quarter of 2022.

This BLA is based on the results of the PATHFINDER clinical trial program, including the pivotal Phase 3 NAVIGATOR trial. In a broad population of patients with uncontrolled asthma receiving medium- to high-dose inhaled corticosteroids (ICS) plus at least one additional controller medication (with or without oral corticosteroids [OCS]), tezepelumab demonstrated superiority over placebo across all primary and key secondary endpoints. In the NAVIGATOR trial, there were no clinically meaningful differences in safety outcomes between the tezepelumab and placebo groups. The results of the NAVIGATOR trial were published in *The New England Journal of Medicine* in May 2021. The trial data demonstrated that all primary and key secondary endpoints were met in the Phase 3 NAVIGATOR clinical trial evaluating patients with uncontrolled severe asthma. Compared with placebo, tezepelumab reduced the annualized asthma exacerbation rate (AAER) by 56% (p<0.001). Notably, in September 2018, the U.S. FDA granted tezepelumab Breakthrough Therapy Designation for the treatment of severe asthma in patients without an eosinophilic phenotype.

Tezepelumab is a potential "first-in-class" drug that blocks the action of thymic stromal lymphopoietin (TSLP). TSLP is an epithelial cytokine positioned at the apex of multiple inflammatory cascades, initiating exaggerated immune responses in allergic, eosinophilic, and other types of airway inflammation associated with severe asthma. The press release states that NAVIGATOR is the first Phase 3 clinical trial to demonstrate benefits in patients with severe asthma by targeting TSLP. (Original text abridged)