Benralizumab Helpful in Severe Eosinophilic Asthma

By David Douglas

Benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, is safe and effective in treatment of severe uncontrolled, eosinophilic asthma, according to two new industry-funded studies.

"Severe asthma affects 5% to 10% of all asthma patients. These patients drive over 50% of the costs of asthma," Dr. J Mark FitzGerald of Vancouver General Hospital, Canada, who was involved in both studies, told Reuters Health by email. "Currently available therapies have limited efficacy. The anti-IL-5 therapies have shown a significant benefit in reducing asthma exacerbations and improving lung function."

Both studies were published online September 5 in The Lancet.

In the first, called CALIMA, Dr. Fitzgerald and colleagues studied 1,306 patients with severe asthma that was not controlled by inhaled medium- to high-dosage corticosteroids plus long-acting beta2-agonists. All had a history of two or more exacerbations in the previous year.

Patients continued receiving their background asthma controller medications at a stable dosage and were randomized to receive 56 weeks of benralizumab 30 mg every four weeks, benralizumab 30 mg every four weeks for the first three doses and then switching to eight-week dosing intervals, or to placebo.

In all, following stratification, 728 patients with baseline blood eosinophil counts of 300 cells/mcl or more were included in the primary analysis population.

Compared with placebo, benralizumab lowered annual exacerbation rates significantly with the four-week regimen (rate ratio, 0.64; p=0.0018) as well as the eight-week regimen (rate ratio, 0.72; p=0.0188).

Both doses also resulted in significant improvement in pre-bronchodilator lung function (FEV1). However total asthma symptom scores were improved only in the eight-week group.

The results of the CALIMA trial "validate the approach of targeting the interleukin-5 receptor alpha to deplete eosinophil counts, reduce asthma exacerbations, improve lung function, and substantially alleviate asthma symptoms of patients with severe, uncontrolled asthma," the researchers write.

In the second study, called SIROCCO, patients had to have had a physician-based diagnosis of asthma for at least one year and at least two exacerbations while on high-dosage inhaled corticosteroids and long-acting beta2-agonists in the previous year.

Patients continued to receive their background asthma controller medications at a stable dosage.

Again they were stratified according to blood eosinophil counts and those with at least 300 cells/mcl were included in the primary analysis population. In all, 1,207 patients were randomized to benralizumab in the same dosages as in the previous study or to placebo.

Over the course of the 48-week study, among the 809 patients in the primary analysis population, the annual exacerbation rate was significantly lower in patients on the four-week regimen (rate ratio, 0.55) and the eight-week regimen (rate ratio, 0.49) compared with those on placebo.

Both benralizumab dosing regimens significantly improved prebronchodilator FEV1 in patients at week 48 compared with placebo. However, as in the previous study, asthma symptoms were improved only in the eight-week group.

In an accompanying editorial, Dr. Mario Castro noted that, similarly to mepolizumab and reslizumab, benralizumab reduced significant asthma exacerbations in patients with a severe eosinophilic phenotype.

"Now we have a third inhibitor of IL-5 for these patients that can be potentially used over two months," Dr. Castro of Washington University School of Medicine, St. Louis, Missouri added in an email to Reuters Health.

AstraZeneca and Kyowa Hakko Kirin funded the studies.

SOURCE: http://bit.ly/2ddjihw, http://bit.ly/2cjtgfv and http://bit.ly/2d4OLlJ

Lancet 2016.

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