Respiratory Trials·org

Asthma · Biologics for severe asthma

SIROCCO randomised trial

Efficacy and safety of benralizumab for patients with severe asthma uncontrolled on high-dosage ICS plus LABA

SIROCCO trial design and results
Design Phase 3, randomised, double-blind, placebo-controlled trial
Treatment Benralizumab 30 mg every 4 weeks or every 8 weeks
Control Placebo
Population 1205 randomised patients with severe uncontrolled asthma; 809 with blood eosinophils of at least 300 cells/µL formed the primary analysis population
Follow-up 48 weeks
Primary endpoint Annual asthma exacerbation rate in patients with eosinophils at least 300 cells/µL
Result Compared with placebo, benralizumab reduced the annual exacerbation rate over 48 weeks when given every 4 weeks (rate ratio 0.55, 95% CI 0.42 to 0.71, p<0.0001) and every 8 weeks (rate ratio 0.49).
Secondary endpoints FEV1, asthma symptom score, safety

These results confirm the efficacy and safety of benralizumab for patients with severe asthma and elevated eosinophils, which are uncontrolled by high-dosage ICS plus LABA, and provide support for benralizumab to be an additional option to treat this disease in this patient population.

The trial authors, in the published abstract

How it has aged

Depletes eosinophils outright by targeting the IL-5 receptor rather than the cytokine, which gives near-complete eosinophil ablation. The eight-weekly schedule was as effective as four-weekly, foreshadowing the dosing-interval question that SWIFT pushed to six months. Its later use in acute exacerbations (ABRA) is a different idea entirely.

Publications

Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β(2)-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial

Bleecker ER, FitzGerald JM, Chanez P, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β(2)-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet 2016 Oct 29;388(10056):2115-2127.

  • 45% reduction in annual exacerbation rate with 4-weekly dosing
  • 51% reduction with 8-weekly dosing
  • Benefit confined to patients with eosinophils of at least 300 cells/µL