Benralizumab demonstrates durable efficacy in patients with severe asthma
The interleukin-5 receptor alpha (IL-5Rα) antagonist benralizumab has demonstrated durable efficacy and safety among patients with severe, uncontrolled eosinophilic asthma in a study reported at the recent European Respiratory Society (ERS) International Congress 2018.
The randomized, double-blind, parallel group phase III BORA study, with 1,926 patients from 447 participating centres in 24 countries, showed that the efficacy and safety profiles of benralizumab were consistent with results reported in the predecessor studies SIROCCO and CALIMA after 2 years. [Busse W, et al, ERS 2018, abstract OA3567; Lancet 2016;388:2115-2127; Lancet 2016;388:2128-2141]
Patients from the SIROCCO and CALIMA trials who were given benralizumab 30 mg every 4 weeks (n=633) or every 8 weeks (n=639) were enrolled in the BORA extension trial and continued treatment. Patients from the SIROCCO and CALIMA trials who received placebo were started on benralizumab 30 mg every 4 weeks (n=320) or every 8 weeks (n=334).
The rates of any and serious adverse events (AEs) during the study period were comparable in BORA (65−71 percent; 10−11 percent) and the SIROCCO/CALIMA studies (71−75 percent; 9−13 percent). Rates of AEs leading to treatment discontinuation were also similar between the BORA (2−3 percent) and SIROCCO/CALIMA studies (2 percent). The rate of death was likewise similar for both BORA and SIROCCO/CALIMA studies (1 percent for both).
“The results of the BORA study provide assurance of the long-term efficacy and safety of benralizumab as add-on maintenance treatment for patients with severe eosinophilic asthma,” commented study lead investigator Professor William Busse from the Division of Allergy and Immunology, University of Wisconsin, Madison, Wisconsin, US.
Similar rates of injection site reactions were demonstrated in the BORA (1−2 percent) and SIROCCO/CALIMA studies (2−3 percent). Positive antidrug antibody (ADA) responses were noted at similar rates in the BORA (8−15 percent) and SIROCCO/CALIMA studies (13−15 percent).
“The presence of ADA was not associated with hypersensitivity and did not affect the responsiveness to benralizumab treatment,” commented Busse.
For patients with baseline blood eosinophil count (BEC) ≥300 cells/µL, the annual exacerbation rates with benralizumab were comparable between the BORA (0.46−0.57) and SIROCCO/CALIMA studies (0.65−0.66).
“For those who continued treatment with benralizumab, lung function was maintained. For those newly treated with benralizumab, lung function improved [mean change from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1) at 68 weeks, 0.131 L for benralizumab every 4 weeks; 0.081 L for benralizumab every 8 weeks],” added Busse.
For patients previously treated with benralizumab, reductions in BEC were maintained. For those who were newly treated, BEC decreased from 400−450 cells/µL to 10 cells/µL with benralizumab every 4 weeks and 200 cells/µL for those treated every 8 weeks.
“Our study showed that patients receiving benralizumab for a second year had safety and tolerability outcomes similar to those who received 1 year of treatment. There were also no new safety signals noted with long-term depletion of BEC. Improvements in exacerbation frequency, lung function and asthma symptoms were maintained up to the second year,” Busse concluded.