Tezepelumab Cuts Severe Asthma Exacerbations by More Than Half, Study Says

A novel biologic for severe asthma reduced exacerbations by 56%, according to a study published Wednesday in The New England Journal of Medicine.

The drug will be discussed further at the ATS 2021 International Conference, which begins this Friday.

Tezepelumab reduced exacerbations by 56% overall and 41% in those with eosinophils less than 300 cells per microliter. It targets thymic stromal lymphopoietin (TSLP), an epithelial-cell–derived cytokine implicated in asthma.

This week, AstraZeneca, which is partnering on the drug with Amgen, submitted a Biologics License Application (BLA) to the FDA.

The phase 3, multicenter, randomized, double-blind, placebo-controlled trial assigned patients aged 12 to 80 years to receive tezepelumab (210 mg) or a placebo subcutaneously every 4 weeks for 52 weeks (529 were assigned to receive tezepelumab and 532 to receive placebo).

The primary end point was the annualized rate of asthma exacerbations over the 52 weeks.

The annualized rate of asthma exacerbations was 0.93 (95% CI, 0.80-1.07) with tezepelumab and 2.10 (95% CI, 1.84-2.39) with placebo (rate ratio [RR], 0.44; 95% CI, 0.37-0.53; P <.001).

For those with a type of asthma referred to as noneosinophilic asthma— a blood eosinophil count of less than 300 cells per microliter—the annualized rate was 1.02 (95% CI, 0.84-1.23) with tezepelumab and 1.73 (95% CI, 1.46-2.05) with placebo (RR, 0.59; 95% CI, 0.46-0.75; P <.001).

TSLP levels are correlated with disease severity, airway obstruction, and resistance to glucocorticoids. The patients in the trial had been on medium or high-dose inhaled glucocorticoids (daily dose of ≥500 μg of fluticasone propionate or equivalent) for at least 12 months and at least 1 additional controller medication, with or without oral glucocorticoids, for at least 3 months before joining the study.

The drug also scored well on secondary end points, including improved lung function, asthma control, and health-related quality of life.

The most common adverse events were nasopharyngitis, upper respiratory tract infection, headache, and asthma (which was more frequently observed in the placebo group); the frequency and type of AEs did not differ significantly between the 2 groups.

In an email to The American Journal of Managed Care®, the lead author of the study, Andrew Menzies-Gow MBBS, PhD, FRCP, director of the Lung Division, deputy medical director, Royal Brompton & Harefield Hospitals, said the drug "has the potential to transform treatment for a broad population of severe asthma patients, regardless of their type of inflammation."

The study was limited by its short time frame and exclusion criteria (such as for patients with some co-existing conditions, as well as smokers). Most of the patients were White adults; in addition, the study had a limited number of adolescents.

Reference

Menzies-Gow A, Corren J, Bourdin A. Tezepelumab in adults and adolescents with severe, uncontrolled asthma. N Engl J Med. 2021; 384(19); 1800-1809.