FDA Grants Priority Review to Tezepelumab for Severe Asthma

Tezepelumab’s biologic license application (BLA) was granted priority review by the FDA for the treatment of severe, uncontrolled asthma, according to AstraZeneca.

Tezepelumab is the first biologic to show a reduction in asthma symptoms, according to phase 3 study results. Tezepelumab is a potential first-in-class human monoclonal antibody that inhibits the action of thymic stromal lymphopoietin (TSLP), a key epithelial cytokine that sits at the top of multiple inflammatory cascades. TSLP is critical in the initiation and persistence of the types of airway inflammation associated with severe asthma.

Tezepelumab was granted priority review by the FDA due to its advantages over current options in the areas of safety improvement, preventing serious conditions, and enhancing patient compliance.1 The agency has set a regulatory decision date during the first quarter of 2022.

The BLA was based on the results of the PATHFINDER clinical trial program, including the phase 3 NAVIGATOR. In clinical trials, tezepelumab demonstrated superiority across every primary and key secondary end point when compared with placebo in a broad population of patients with uncontrolled asthma. Participants received tezepelumab in addition to standard-of-care treatment with medium- or high-dose inhaled corticosteroids (ICS) plus at least 1 additional controller medicine with or without oral corticosteroids (ICS).

The NAVIGATOR study included adults 18 to 80 years old and adolescents aged 12 to 17-years with severe, uncontrolled asthma who were receiving standard of care. The trial population included approximately equal proportions of patients with high and low blood eosinophil counts.

The study was conducted over 52 weeks and patients were grouped by baseline blood eosinophil count, fractional exhaled nitric oxide level, and serum specific immunoglobin E status (perennial allergen sensitivity positive or negative). The testing involved analyzing a patient’s blood and exhaled air.

The trial comprised a 5- to 6-week screening period, a 52-week treatment period, and a 12-week post-treatment follow-up period. All patients received their prescribed controller medicines without change throughout the trial. Key secondary end points included the effect of tezepelumab on lung function, asthma control, and health-related quality of life.

There were no differences in safety results between placebo and tezepelumab in trials. The most frequently reported adverse events with tezepelumab were nasopharyngitis, upper respiratory tract infection, and headache.

Severe asthma has been rising, however, some patients are warned against the use of biopharmaceuticals or biologics.1 Patients with severe asthma are severely affected by their condition. “Tezepelumab has demonstrated reductions in exacerbations irrespective of blood eosinophil counts, allergy status and fractional exhaled nitric oxide, and has the potential to transform treatment for a broad population of severe asthma patients,” said Mene Pangalos, executive vice president of BioPharmaceuticals R&D.

Approximately 10% of patients with asthma have severe asthma. Despite the use of inhaled asthma controller medicine, currently available biologic therapies and OCS, many severe asthma patients remain uncontrolled. Due to the complexity of severe asthma, many patients have unclear or multiple drivers of inflammation and may not qualify for or respond well to current biologic medicine.

Severe, uncontrolled asthma is debilitating with patients experiencing frequent exacerbations, significant limitations on lung function, and reduced quality of life. Patients with severe asthma are at an increased risk of mortality and compared to patients with persistent asthma have twice the risk of asthma-related hospitalizations. There is also a significant socioeconomic burden, with these patients accounting for 50% of asthma-related costs.

Tezepelumab received breakthrough therapy designation for patients with severe asthma without an eosinophilic phenotype in September 2018.

Reference

1. Tezepelumab regulatory submission accepted and granted FDA Priority Review in the US for the treatment of patients with asthma. News release. AstraZeneca; July 8, 2021. Accessed July 12, 2021. https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/tezepelumab-granted-fda-priority-review-for-asthma.html.