Tezepelumab for Severe Asthma Meets Phase 3 Primary Endpoint

The novel monoclonal antibody could bring relief to millions of persons with severe, uncontrolled asthma, including those with a low eosinophil phenotype.

Tezepelumab, an investigational treatment for patients with severe uncontrolled asthma, today met its primary endpoint in a phase 3 clinical trial, according to a statement from collaborating developers AstraZeneca and Amgen.

Tezepelumab is a potential first-in-class human monoclonal antibody that inhibits the action of thymic stromal lymphopoietin (TSLP), an epithelial cytokine that acts at the top of several inflammatory cascades and is known to be critical in initiation and persistence of airway inflammation associated with severe asthma, according to the companies' statement. NAVIGATOR is the first Phase III trial to show benefit in severe asthma by targeting TSLP.

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

The NAVIGATOR trial population included approximately equal proportions of patients with high (≥ 300 cells/µL) and low (<300 cells/µL) blood eosinophil counts.In the subgroup of patients with baseline eosinophil counts <300 cells/cells/µL, the trial also met the primary endpoint, with tezepelumab demonstrating a statistically significant and clinically meaningful reduction in AAER.

Importantly, similar reductions in AAER were seen in the subgroup of patients with baseline eosinophil counts <150 cells/µL, a group not currently well served by existing treatments for severe asthma which are approved for patients with eosinophilic, vs non-eosinophilic, asthma.

“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," said Professor Andrew Menzies-Gow, director of the Lung Division, Royal Brompton Hospital, London, UK, principal investigator, NAVIGATOR Phase III trial, in the published statement.

"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.”

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

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.