Benralizumab (AstraZeneca/MedImmune), an investigational anti-eosinophil monoclonal antibody, was well tolerated and achieved the primary endpoint in two pivotal phase 3 trials, demonstrating significant reductions in the annual asthma exacerbation rate compared with placebo.
The SIROCCO and CALIMA trials are part of the WINDWARD clinical development program in asthma, which consists of six phase 3 studies in 3,068 patients in 26 countries. The two randomized, double-blind, parallel-group, placebo-controlled trials were designed to evaluate the efficacy and safety of a fixed 30-mg dose of benralizumab administered subcutaneously in patients with a history of asthma exacerbations and uncontrolled asthma receiving inhaled corticosteroids (ICS) plus a long-acting beta2-agonist (LABA) with or without an oral corticosteroid and additional asthma controllers.
A total of 2,511 patients (1,205 in SIROCCO and 1,306 in CALIMA) were randomly assigned to receive benralizumab 30 mg every four weeks for the first three doses followed by 30 mg every eight weeks, or placebo. The primary analysis population included patients on high-dose ICS plus a LABA with a baseline blood eosinophil count greater than or equal to 300 cells/mcL.
Eosinophils are the biological effector cells that drive inflammation and airway hyper-responsiveness in approximately 50% of asthma patients, leading to frequent exacerbations, impaired lung function, and reduced quality of life. Benralizumab is an anti-eosinophil monoclonal antibody that depletes eosinophils via antibody‐dependent cell-mediated cytotoxicity (ADCC), the process by which natural killer cells are activated to target eosinophils. Benralizumab depletes eosinophils in the bone marrow, blood, and target tissue.
The drug is expected to be submitted for FDA review in the second half of 2016.
Source: AstraZeneca; May 17, 2016.