Patients with severe, uncontrolled asthma receiving a 1-year course of benralizumab injections had significantly reduced rates of asthma-related exacerbations, according to data from two phase 3 trials published in The Lancet and presented at the 2016 European Respiratory Society International Congress.
“Patients with severe, uncontrolled asthma have very few treatment options once they are already taking high-dose inhaled corticosteroids (ICS) and long-acting beta agonists (LABA),” Eugene Bleecker, MD, lead researcher of the SIROCCO trial from Wake Forest School of Medicine said. “Two drugs are currently approved for the treatment of severe, uncontrolled asthma (mepolizumab and reslizumab), but both target the IL-5 molecule directly, rather than the receptor.”
The CALIMA and SIROCCO trials both evaluated the safety and efficiency of benralizumab — an antibody that targets the IL-5 receptor, therefore, having the ability to diminish eosinophils directly — as an additional therapy for patients with the most severe form of asthma.
Researchers of the CALIMA trial enrolled 1,306 patients with severe asthma between 12 years and 75 years of age, who were already taking ICS and LABA and who had at least two exacerbations within the last year.
Participants were randomized into three groups and received 30 mg injections of benralizumab every 4 weeks or 8 weeks or received a placebo. Participants were followed for 56 weeks.
Results of the CALIMA trial indicated that benralizumab-treated patients had a 28% to 36% reduction in the number of asthma-related exacerbations experienced in comparison to those receiving a placebo. Patients treated every 4 weeks went from 2.8 exacerbations per year to 0.60. Those treated every 8 weeks reduced from 2.7 to 0.66 exacerbations. The placebo group reduced from 2.8 to 0.93.
Overall, improved lung function was associated with benralizumab treatment. An increased total asthma score was observed only in patients receiving benralizumab every 8 weeks.
The most documented adverse events were nasopharyngitis (benralizumab, 20%; placebo, 21%) and worsening asthma (benralizumab, 12%; placebo 15%). Other serious adverse events related to treatment included urticaria (n = 1) and asthma and herpes zoster (n = 2) within the benralizumab group, as well as non-cardiac chest pain (n = 1) within the placebo group.
Patients in the SIROCCO trial (n = 1,209) were randomly allocated into three similar groups and followed for 48 weeks. Only participants with high eosinophil counts were evaluated (n = 809).
Results of the SIROCCO trial showed that compared to the placebo group, the benralizumab group had a 45-51% reduction in the number of exacerbations experienced (benralizumab every 4 weeks, reduction from 3.0 to 0.73 exacerbations per year; every 8 weeks, 2.8 to 0.65; placebo, 3.1 to 1.33).
Improved lung function and total asthma score was detected in patients receiving benralizumab injections every 8 weeks.
“Eosinophil counts were nearly completely depleted by week 4 of treatment [with benralizumab],” according to Bleecker.
Worsening asthma and nasopharyngitis were also the most common adverse events in the SIROCCO trial. Worsening asthma was seen in 13% of patients in the benralizumab group and 19% in the placebo group. Nasopharyngitis was seen in 12% of benralizumab-treated patients and 12% of placebo-treated patients.
Within the benralizumab group, patients reported other serious adverse events including allergic granulomatous (n = 1), panic attack (n = 1) and paresthesia (n = 1), while those in the placebo group reported injection-site erythema (n = 1).
“The results from both trials indicate that benralizumab treatment once every 4 or 8 weeks decreased eosinophil counts, reduced asthma exacerbations, and improved lung function for patients with severe, uncontrolled asthma with eosinophilia,” J. Mark FitzGerald, MB, MCh, BAO, MD, FRCPI, FRCPC, FACCP, FACP, lead researcher of the CALIMA trial from The Lung Centre at Vancouver Coastal Health and the University of British Columbia. “Additional therapeutic options to control severe asthma are urgently needed and our findings support the use of benralizumab as an add-on therapy for the treatment of severe asthma with persistent eosinophilia.” – by Alaina Tedesco
Disclosure: Researchers of the CALIMA and SIROCCO trials report funding by AstraZeneca and Kyowa Hakko Kirin.