Tezepelumab NAVIGATOR trial in severe, uncontrolled asthma patients meets primary endpoint

On Nov 10, 2020

Amgen and AstraZeneca announced positive topline results from the Phase 3 NAVIGATOR trial in which the investigational medicine tezepelumab demonstrated a statistically significant reduction in exacerbations compared to placebo in patients with severe asthma.

The NAVIGATOR trial met the primary endpoint with tezepelumab added to standard of care (SoC) demonstrating a statistically significant and clinically meaningful reduction compared to placebo plus SoC in the annualized asthma exacerbation rate (AAER) over 52 weeks in the overall patient population. SoC was medium- or high-dose inhaled corticosteroids (ICS) plus at least one additional controller medication with or without oral corticosteroids (OCS).

In the subgroup of patients with baseline eosinophil counts less than 300 cells per microliter, the trial met the primary endpoint with tezepelumab demonstrating a statistically significant and clinically meaningful reduction in AAER. Similar reductions in AAER were observed in the subgroup of patients with baseline eosinophil counts less than 150 cells per microliter.

The significant exacerbation rate reductions demonstrated with tezepelumab in patients with baseline eosinophil counts less than 300 cells per microliter support the U.S. Food and Drug Administration Breakthrough Therapy Designation granted to tezepelumab in Sept. 2018 for patients with severe asthma, without an eosinophilic phenotype.

Tezepelumab was very well tolerated in patients with severe asthma. Preliminary analyses show no clinically meaningful differences in safety results between the tezepelumab and placebo groups. Results from the NAVIGATOR trial will be presented at an upcoming medical meeting.

Tezepelumab is a potential first-in-class medicine that blocks the action of thymic stromal lymphopoietin (TSLP), an epithelial cytokine that plays a key role across the spectrum of asthma inflammation.^1,2 NAVIGATOR is the first Phase 3 trial to show benefit in severe asthma by targeting TSLP.

“We are absolutely thrilled with the topline results of the NAVIGATOR study in this broad population of patients with severe asthma, regardless of eosinophil count,” said David M. Reese, M.D., executive vice president of Research and Development at Amgen. “Tezepelumab represents a potential new class of biologics that could enable us to treat severe asthma at the top of the inflammatory cascade, addressing a high unmet need among the millions of patients living with severe asthma throughout the world. Tezepelumab has the potential to revolutionize care with efficacy demonstrated even in patients with a low eosinophil count.”

Professor Andrew Menzies-Gow, director of the Lung Division, Royal Brompton Hospital, London, UK, and principal investigator of the NAVIGATOR trial said: “Due to the complex nature of severe asthma, many patients continue to face debilitating asthma 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.”