Amgen and AstraZeneca Announce Positive Phase 3 NAVIGATOR Trial Results for Tezepelumab in Severe Asthma

On November 9, Amgen and AstraZeneca jointly announced that tezepelumab, a monoclonal antibody therapy targeting thymic stromal lymphopoietin (TSLP) co-developed by the two companies, achieved positive top-line results in the Phase 3 NAVIGATOR clinical trial in patients with severe asthma. Compared with placebo, tezepelumab significantly reduced disease exacerbations in patients with severe asthma.

Asthma is a complex, heterogeneous disease affecting an estimated 339 million people worldwide, 10% of whom have severe asthma. However, many patients with severe asthma respond inadequately to currently available biologics and oral corticosteroids, resulting in uncontrolled symptoms. Uncontrolled severe asthma is debilitating, characterized by frequent exacerbations, significant impairment of lung function, and reduced quality of life.

Multiple inflammatory pathways are involved in the pathogenesis of asthma. T2 inflammation-driven asthma, including eosinophilic asthma, accounts for approximately two-thirds of patients with severe asthma. However, many patients do not meet the criteria for eosinophilic or allergic asthma and may have multiple inflammatory drivers.

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

▲TSLP influences immune responses in various immune cells (Image source: Reference [2])

In the NAVIGATOR trial, tezepelumab met the primary endpoint, demonstrating a statistically and clinically significant reduction in the annualized asthma exacerbation rate (AAER) when combined with standard of care (SoC), compared to placebo plus SoC.

In the subgroup of patients with baseline eosinophil counts below 300 cells/μL, tezepelumab also met the primary endpoint, and a similar reduction in AAER was observed in the subgroup with baseline eosinophil counts below 150 cells/μL. These data demonstrate that tezepelumab significantly reduces disease exacerbations across a broad population of patients with severe asthma.

References:

[1] Tezepelumab NAVIGATOR Phase 3 Trial Met Primary Endpoint Of A Statistically Significant And Clinically Meaningful Reduction In Exacerbations In A Broad Population Of Patients With Severe Asthma. Retrieved November 10, 2020, https://www.amgen.com/media/news-releases/2020/11/tezepelumab-navigator-phase-3-trial-met-primary-endpoint-of-a-statistically-significant-and-clinically-meaningful-reduction-in-exacerbations-in-a-broad-population-of-patients-with-severe-asthma/

[2] Comeau & Ziegler. (2009). The influence of TSLP on the allergic response. Mucosal Immunology, https://doi.org/10.1038/mi.2009.134

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