Treatment using tezepelumab in the NAVIGATOR Phase 3 clinical trial was well tolerated in patients with severe asthma


The new AstraZeneca Corprate HQ under construction in Cambridge UK. (Credit: D Wells/Wikipedia.)

AstraZeneca and Amgen announced that Phase 3 NAVIGATOR trial of tezepelumab, their potential new medicine for severe uncontrolled asthma, has met the primary endpoint.

Tezepelumab, when added to standard of care (SoC), showed statistically significant and clinically meaningful reduction in the annualised asthma exacerbation rate (AAER), compared to placebo added to SoC.

Medium- or high-dose inhaled corticosteroids (ICS) combined with at least one additional controller medication, regardless of oral corticosteroids (OCS) is considered as SoC.

Tezepelumab is an advanced human monoclonal antibody developed by Amgen and AstraZeneca under collaboration agreement initially signed in 2012.

The drug works by inhibiting the activity of thymic stromal lymphopoietin (TSLP), an epithelial cytokine that plays a crucial role in allergic, eosinophilic and other types of inflammation related to severe asthma.

The companies updated their initial agreement in early 2020, pursuant to which Amgen and AstraZeneca will jointly commercialise tezepelumab. Amgen will sell the drug in the US, while AstraZeneca in Canada.

AstraZeneca BioPharmaceuticals R&D executive vice president Mene Pangalos said: “Tezepelumab works differently from any other asthma biologic medicine and targets multiple inflammatory pathways that contribute to asthma symptoms and exacerbations.

“Building on the broad efficacy previously seen with tezepelumab, these are exciting data that bring us one step closer to delivering a medicine to severe asthma patients, including those with low eosinophil counts.”

Phase 3 NAVIGATOR is a randomised, double-blinded, placebo-controlled trial evaluating tezepelumab in adults and adolescents with severe, uncontrolled asthma, taking ICS plus at least one additional controller medication.

Severe asthma is a debilitating condition, where patients experience symptoms despite the use of high-dose asthma controller medicines, biologic therapies and OCS.

The trial enrolled almost equal proportions of patients with high and low blood eosinophil counts, and all patients received prescribed controller medication across the trial.

The primary efficacy endpoint was the annualised asthma exacerbation rate at 52 weeks, while the key secondary endpoints include the effect of tezepelumab on lung function, asthma control and health-related quality of life.

In the study, tezepelumab was well tolerated in patients with severe asthma, with preliminary analyses showing no clinically meaningful differences in safety results compared to placebo.

NAVIGATOR Phase 3 trial professor Andrew Menzies-Gow said: “Due to the complex nature of severe asthma, many patients continue to face debilitating symptoms despite receiving standard of care inhaled medicines and currently approved biologics.

“Today’s ground-breaking results show that tezepelumab has the potential to transform care for a broad population of severe asthma patients who are underserved today, including those without an eosinophilic phenotype.”