As an add-on therapy for patients with severe, uncontrolled asthma and elevated blood eosinophil counts, benralizumab significantly reduced annual exacerbation rates and was generally well tolerated in the patient population, a recent study found. The randomized, double-blind, placebo-controlled phase 3 trial (CALIMA) enrolled 2,505 patients between August 21, 2013, and March 16, 2015 aged 12 to 75 years with severe asthma uncontrolled by medium-dosage to high-dosage inhaled corticosteroids, plus long-acting beta-2 agonists and a history of 2 or more exacerbations in the previous year. Patients were randomly assigned 1:1:1 to receive 56 weeks of benralizumab 30 mg every 4 weeks (n=425; Q4W), benralizumab 30 mg every 8 weeks (n=441; Q8W), or placebo (n=440). Researchers found:

• Significantly lower annual exacerbation rates (approximately 35% decrease) were observed with the Q4W regimen and Q8W regimen compared with placebo.

• Benralizumab also significantly improved pre-bronchodilator FEV₁ (Q4W and Q8W) and total asthma symptom score (Q8W only).

• The most common adverse events were nasopharyngitis and worsening asthma.

Citation: Fitzgerald JM, Bleecker E, Nair P, et al. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. [Published online ahead of print September 4, 2016]. Lancet. doi:10.1016/S0140-6736(16)31322-8.

Commentary: Benralizumab is a humanised, glycosolated, anti-interleukin-5 receptor α monoclonal antibody that induces direct, rapid, and nearly complete depletion of eosinophils. Interleukin-5 is a key mediator of eosinophil activation, and interference leads to depletion of eosinophils. Since some patients have primarily allergic asthma, often characterized by elevated eosinophil counts, and eosinophils are felt to be important in causing exacerbations though degranulation and subsequent wheezing when antigens are present, monoclonal antibodies such as benralizumab have been developed to decrease eosinophils and to in turn decrease asthma exacerbation. This study supports this hypothesis and shows benralizumab to be effective in treating eosinophil predominant asthma. —Neil Skolnik, MD