Benralizumab fails to decrease COPD exacerbations

Benralizumab, a monoclonal antibody to an interleukin-5 receptor that reduces eosinophil counts in the sputum and the blood and has been used to treat asthma, failed to decrease acute exacerbations of chronic obstructive pulmonary disease in an industry-sponsored phase II clinical trial reported at the European Respiratory Society International Congress 2014.

In what they described as the first study of a biologic treatment for eosinophilic COPD, researchers found that benralizumab rapidly depleted both sputum and blood eosinophils "to a much greater extent than did inhaled or oral corticosteroids in other studies," but nonetheless failed to fulfill the primary endpoint of reducing the rate of acute exacerbations, Dr. Christopher E. Brightling said in a paper simultaneously presented at the Congress and published online in Lancet (2014 [doi:10.1016/S2213-2600(14)70187-0]).

During a 3-year period, the double-blind trial enrolled 101 adults aged 45-80 years who were current or past smokers and had moderate to severe COPD. They were treated at 26 medical centers in the United Kingdom, Poland, Germany, Canada, the United States, Denmark, and Spain. These participants were randomly assigned to receive a total of eight subcutaneous injections of 100 mg benralizumab (51 patients) or a matching placebo (50 patients) at intervals over the course of 48 weeks, said Dr. Brightling of the National Institute for Health Research Respiratory Biomedical Research Unit, University of Leicester, England.

The primary endpoint, the annualized rate of acute COPD exacerbations at week 56, was 0.95 with benralizumab and 0.92 with placebo, a nonsignificant difference. There also was no significant difference between the two study groups in the need for oral corticosteroids or intravenous antibiotics, nor in the rate of hospitalization.

Benralizumab did deplete blood and sputum eosinophils at the first assessment of these outcomes, an effect that persisted throughout the treatment period and well beyond. It also produced clinically significant improvements in both prebronchodilator and postbronchodilator forced expiratory volume in 1 second, from the first assessment of these outcomes until week 80 –32 weeks after the final dose was administered.

The benralizumab group had a higher rate of serious adverse events than did the placebo group, but none of those events were considered to be drug related. No hypersensitivity reactions or immune-complex disorders occurred.

This study was funded by MedImmune, maker of benralizumab, which also participated in study design, data analysis, and manuscript preparation. Dr. Brightling reported receiving grants from MedImmune, GlaxoSmithKline, Roche, Novartis, and Chiesi; his associates reported ties to numerous industry sources.