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Positive Phase 3 Results for Benralizumab in Severe Asthma

Regulatory submissions are planned for the U.S. and E.U. later in 2016

Results from pivotal phase 3 trials have demonstrated that adding benralizumab to standard-of-care medicine significantly reduced exacerbations and improved lung function and asthma symptoms in patients with severe asthma and an eosinophilic phenotype.

The SIROCCO and CALIMA trials evaluated the effect of benralizumab 30 mg, administered in four-week or eight-week regimens, as add-on therapy to standard-of-care medicine across primary and key secondary endpoints. Results showed:

  • Reductions in the annual rate of asthma exacerbations (up to 51%)
  • Improvement in lung function (change in forced expiratory volume in one second [FEV1] of up to 159 mL), which was seen at four weeks after the first benralizumab dose and sustained throughout the treatment period
  • Improvement in asthma symptoms, such as wheeze, cough, chest tightness, and shortness of breath

The outcomes were demonstrated for the eight-week dosing regimen, with no additional benefit observed with four-week dosing, which may support less-frequent dosing. In addition, post-hoc analysis showed greater improvements in exacerbation rate reduction, FEV1, and total asthma symptom scores in patients with a history of more frequent asthma exacerbations (three or more in the previous year).

The adverse event frequency was similar between benralizumab-treated patients versus placebo-treated patients for both SIROCCO and CALIMA (72% and 74% for all benralizumab-treated patients versus 76% and 78% for placebo-treated patients in SIROCCO and CALIMA, respectively). The most common (5% or greater) adverse events in benralizumab-treated patients observed in SIROCCO were asthma, nasopharyngitis, upper respiratory infection, headache, bronchitis, sinusitis, influenza, and pharyngitis; in CALIMA they were nasopharyngitis, asthma, bronchitis, upper respiratory tract infection, headache, and sinusitis.

Severe uncontrolled asthma is a debilitating and potentially fatal form of the disease, in which patients experience frequent exacerbations every year and have significant limitations in lung function and quality of life. Uncontrolled asthma can lead to a dependence on oral corticosteroids, with systemic steroid exposure leading to serious and irreversible adverse effects.

Benralizumab is an anti-eosinophil monoclonal antibody that induces direct, rapid, and near-complete depletion of eosinophils, with an onset of action within 24 hours as confirmed in early phase 1/2 trials. 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 asthma symptoms.

Results of the trials were presented at the European Respiratory Society International Congress 2016 in London.

Source: AstraZeneca; September 5, 2016.

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