Severe Asthma Drug Shows Promise
Benralizumab led to a significant reduction in the use of oral corticosteroids for patients with severe, uncontrolled eosinophilic asthma.
Treatment with benralizumab led to a meaningful 75% reduction in the use of oral corticosteroids from baseline for patients with severe, uncontrolled eosinophilic asthma, according to findings from the phase 3 ZONDA trial presented at the 2017 ATS International Conference and simultaneously published in the New England Journal of Medicine.
In addition to the reduction in steroid use, treatment with the anti-interleukin-5 receptor α monoclonal antibody benralizumab every 8 weeks reduced annual exacerbation rates by 70% versus placebo (rate ratio, 0.30; 95% CI, 0.17-0.53; P <.001). Moreover, benralizumab every 8 weeks reduced the rate of exacerbations requiring emergency room visits or hospitalizations by 93% compared with placebo (rate ratio, 0.07; 95% CI, 0.01-0.63; P = .02).
“Benralizumab showed an impressive clinical efficacy by reducing exacerbations rate by up to 70% at the same time enabling patients with severe asthma to significantly lower their prednisone dose and maintain their lung function," lead investigator Parameswaran Nair, MD, PhD, professor of Respiratory Medicine at McMaster University in Hamilton, Canada, said in a statement. "This is likely due to its unique mechanism of action of inhibiting the receptor for interleukin-5 and potentially depleting blood and airway eosinophils.”
The phase 3 ZONDA trial randomized patients to receive placebo (n = 75) or subcutaneous benralizumab at 30-mg every 4 weeks (n = 72) or every 8 weeks (n = 73). The mean age of patients was approximately 50 years and the median time since asthma diagnosis ranged from 10.5 to 16.3 years. The mean steroid dose was 1232 μg/day in the placebo group and 1033 μg/day and 1192 μg/day in the every 4-week and every 8-week groups. Overall, nearly 60% of patients were predicted to have a normal value for forced expiratory volume 1 second (FEV1).
A reduction in steroid use of 90% or more was enjoyed by 33% of patients in the benralizumab every 4-week group and for 37% of those in the every 8-week group compared with just 12% in the placebo arm. Fifty-three percent, 51%, and 20% of patients in the benralizumab 4-week, 8-week, and placebo arms reduced their steroid intake by 75% or more. Patients were 4 times more likely to reduce their steroid use in the benralizumab arms.
In the 4-week group, the annual exacerbation rate was reduced by 55% compared with placebo (P = .003). Reductions in exacerbations requiring emergency room visits or hospitalizations were not improved significantly in the 4-week arm (rate ratio, 0.44; 95% CI, 0.13-1.49). There was no difference between FEV1 rates between the benralizumab regimens and placebo.
At least 1 adverse event (AE) was experienced by 83% of those in the placebo arm and in 68% and 75% of those in the 4-week and 8-week benralizumab arms, respectively. The most frequent AEs were nasopharyngitis (17% of patients), worsening asthma (13%), and bronchitis (10%). Serious AEs were experienced by 19% of those in the placebo group and in 10% of patients in each of the benralizumab arms.
"Frequent or long-term use of systemic corticosteroids can lead to potentially life-threatening complications, including osteoporosis, diabetes, cardiovascular disease and adrenal suppression," said Nair. "We need new, safe therapies that would replace the need for systemic corticosteroids for patients with severe asthma."
Data from the ZONDA trial were submitted to the FDA along with findings from the phase 3 SIROCCO and CALIMA trials, which showed similar benefits for benralizumab in patients with severe asthma. These studies demonstrated a clear ability for benralizumab to reduce annual exacerbation rates. The FDA is expected to decide regarding benralizumab for severe asthma in the fourth quarter of 2017.