Amgen, AstraZeneca Report Phase 3 NAVIGATOR Trial of Tezepelumab Meets Primary Endpoint in Patients with Severe Asthma

Amgen, AstraZeneca Report Phase 3 NAVIGATOR Trial of Tezepelumab Meets Primary Endpoint in Patients with Severe Asthma

Amgen and AstraZeneca  announced positive results from NAVIGATOR, a phase 3 trial evaluating tezepelumab versus placebo, both added to standard of care (SOC), in adults (18–80 years old) and adolescents (12–17 years old) with severe, uncontrolled asthma. Tezepelumab plus SOC demonstrated a statistically significant reduction in exacerbations compared to placebo plus SOC. The trial also met the primary endpoint in patients with low levels of eosinophils. Full results from NAVIGATOR will be presented at an upcoming medical meeting.

NAVIGATOR is part of the Phase 3 PATHFINDER program, which also includes SOURCE, as well as additional planned mechanistic and long-term safety trials.

NAVIGATOR is a randomized, double-blinded, placebo-controlled trial in adults (18–80 years old) and adolescents (12–17 years old) with severe, uncontrolled asthma, who were receiving treatment with medium- or high-dose ICS plus at least one additional controller medication with or without OCS (standard of care). The trial population included approximately equal proportions of patients with high (≥ 300 cells/µL) and low (< 300 cells/µL) blood eosinophil counts. 

The trial met the primary endpoint with tezepelumab added to 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. 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.

Amgen and AstraZeneca entered into a collaboration tezepelumab in 2012, which was updated in 2020. 

About Tezepelumab
Tezepelumab is a human monoclonal antibody that acts on the airway epithelium, which is the first point of contact for viruses, allergens, pollutants, and other environmental toxins. Specifically, tezepelumab targets and blocks TSLP, a key epithelial cytokine that sits at the top of multiple inflammatory cascades and initiates an overreactive immune response to allergic, eosinophilic and other types of airway inflammation associated with severe asthma.

TSLP is released in response to multiple triggers associated with asthma exacerbations, including allergens, viruses and other airborne particles. Expression of TSLP is increased in the airways of patients with asthma and has been correlated with disease severity. Blocking TSLP may prevent the release of pro-inflammatory cytokines by immune cells, resulting in the prevention of asthma exacerbations and improved asthma control. By working at the top of the cascade, tezepelumab helps stop inflammation at the source and has the potential to treat a broad population of severe asthma patients.

About Severe Asthma

Asthma is a complex and heterogeneous disease affecting an estimated 339 million people worldwide. Approximately 10% of asthma patients have severe asthma. Yet, many severe asthma patients have an inadequate response to currently available biologics and oral corticosteroids and thus fail to achieve asthma control. Severe, uncontrolled asthma is debilitating with patients experiencing frequent exacerbations, significant limitations on lung function and a reduced quality of life. Multiple inflammatory pathways are involved in the pathogenesis of asthma. Eosinophilic asthma, and more broadly, T2 inflammation-driven asthma, accounts for about two-thirds of patients with severe asthma. These patients are typically characterized as having elevated levels of inflammatory biomarkers, including blood eosinophils, serum IgE and fractional exhaled nitric oxide (FeNO). However, many patients do not fit the criteria for eosinophilic or allergic asthma, may have unclear or multiple drivers of inflammation, and may not qualify for or respond well to a current biologic medicine.