A new ‘precision medicine’ drug—benralizumab—improved symptoms and reduced exacerbations by as much as 51% in patients with severe, uncontrolled eosinophilic asthma, according to two new Phase III clinical trials.
Results of these trials, which included more than 2,500 patients combined, were presented September 5, 2016 at the European Respiratory Society International Congress in London, and published simultaneously in The Lancet Respiratory Medicine.
For patients with severe asthma and elevated eosinophil counts, high-dose inhaled corticosteroids and long-acting β2-agonists often fail to control their symptoms. Benralizumab targets the interleukin-5 (IL-5) receptor, causing eosinophil apoptosis. These two trials—named SIROCCO and CALIMA—tested the safety and efficacy of benralizumab in severe asthma patients with blood eosinophil counts of 300 cells per μL or greater.
“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,” said lead author of the CALIMA trial, J. Mark FitzGerald, MD, Director of the Centre for Heart and Lung Health at Vancouver Coastal Health Research Institute, in Vancouver, BC, Canada.
“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,” Dr. FitzGerald said.
In these two clinical trials, researchers at hundreds of sites around the world randomly assigned severe asthma patients to placebo or to one of two treatment arms: 30 mg subcutaneous injection of benralizumab every 4 weeks, or the same dose every 8 weeks (with the first three doses 4 weeks apart). Subjects in the SIROCCO trial were treated for 48 weeks and those in CALIMA were treated for 56 weeks.
Results showed that add-on therapy with benralizumab decreased patients’ annual asthma exacerbation rate by as much as 36% (in the CALIMA trial) to as much as 51% (in the SIROCCO trial) compared to placebo. Benralizumab also significantly improved lung function and, when administered every 8 weeks, significantly improved patient-reported asthma symptoms.
“These findings indicate that the clinical benefit obtained from benralizumab translates into better asthma control and improved quality of life,” said lead author of SIROCCO trial, Eugene R. Bleecker, MD, Director of the Center for Genomics and Personalized Medicine Research at Wake Forest Baptist Medical Center, Winston-Salem, NC. “By targeting the IL-5 receptor, benralizumab depletes eosinophils directly, and our studies show that eosinophil counts were nearly completely depleted by week 4 of treatment.”
The overall results showed that benralizumab dosed every 8 weeks (Q8W) proved equally or more effective than benralizumab dosed every 4 weeks (Q4W).
In a related commentary, Mario Castro, MD, MPH, and Leonard Bacharier, MD, of Washington University School of Medicine in St. Louis, MO, wrote: “Given the efficacy of Q8W dosing on exacerbations, symptom scores, asthma control, and quality of life, and the economical savings of using half the amount of drug suggests a potential advantage to this dosing regimen over Q4W dosing. Additionally, the less frequent dosing of anti-interleukin-5 might allow one to consider using these biologics earlier in the course of the disease, and in children.”
AstraZeneca, the manufacturer of the drug, expects to submit benralizumab for FDA approval later in 2016.
Trials were funded by AstraZeneca and Kyowa Hakko Kirin.