Oral corticosteroid-dependent patients with severe, uncontrolled asthma who were treated with benralizumab were more than 4 times as likely to reduce their oral corticosteroid (OCS) dose than those in a placebo group, according to a new study published in the New England Journal of Medicine.
The findings were also simultaneously presented at the American Thoracic Society (ATS) 2017 International Congress in May.
Benralizumab is a biologic—a human monoclonal antibody—directed against the interleukin-5 receptor (IL-5Ra) that induces direct, rapid, and near complete depletion of eosinophils via antibody-dependent cell-mediated cytotoxicity (ADCC).
According to Frank Trudo, M.D., brand medical lead, respiratory, AstraZeneca U.S., 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.
The purpose of the ZONDA trial was to assess the effect of benralizumab, compared to that of placebo, on the reduction in the OCS dose while maintaining asthma control in systemic corticosteroid-dependent patients with severe refractory asthma with elevated blood eosinophils.
ZONDA was designed as a 28-week, randomized, double-blind, parallel-group, placebo-controlled, multicenter phase 3 study that included 220 adult patients with severe uncontrolled asthma requiring treatment with high-dosage inhaled corticosteroids (ICS) plus a long-acting beta agonist (LABA) and chronic OCS with blood eosinophil counts of at least 150 cells per microliter, explained Trudo.
Patients were randomly assigned to receive benralizumab 30 mg every 8 weeks subcutaneously (SC) (after the initial 4-week dosing regimen for the first three doses), benralizumab 30 mg every 4 weeks SC, or placebo SC. Patients’ OCS doses were optimized and maintained during the 4-week induction phase and in the subsequent reduction phase (weeks 4-24), daily OCS doses were reduced by 2.5-5.0 mg at 4-weekly intervals.
According to Trudo, ZONDA achieved its primary efficacy objective, with a median reduction in OCS dose of 75% for patients treated with benralizumab versus 25% with placebo. Furthermore, patients on the 8-week dosing regimen demonstrated 70% reduction in overall annual asthma exacerbation rate compared with placebo, and a 93% reduction in exacerbations requiring emergency room visits or hospitalizations compared to placebo.
“Oral corticosteroid reduction is a pivotal question in severe asthma treatment due to the potential for serious and irreversible adverse effects caused by the use of chronic systemic steroids,” said Trudo. “The goal of any asthma treatment is to get the patient under control and reduce the risk of exacerbation, in addition to affording the patient the ability to breathe better.”
The price of benralizumab has not yet been established, but according to Tosh Butt, vice president, respiratory, AstraZeneca U.S., AstraZeneca’s approach to developing the price of medications takes into account many factors and is subject to a rigorous data analytics process and thus benralizumab will be priced to ensure appropriate patients have access to therapy.