Benralizumab Maintains Safety, Efficacy for Asthma in BORA Phase 3 Extension

William Busse, MD

Two years of new safety data from the BORA phase 3 extension study corroborate results from previous clinical trials and suggest that benralizumab (Fasenra/AstraZeneca) safely reduces exacerbations and improves lung function over a 2-year period in patients with severe, uncontrolled eosinophilic asthma.

Safety Profile

According to the new data, the 2 years of safety results confirm that observations from the first year of benralizumab treatment continued through the second year of treatment, and that no new consequences of long-term eosinophil depletion occurred.In the BORA study, the incidence of adverse events, including opportunistic infections, were similar during the first and second year of treatment. The most common adverse events in all groups included in the study were viral upper respiratory tract infection (14-15%) and worsening asthma (7-10%). The most common serious adverse events were worsening asthma (3-4%) pneumonia (<1% to 1%) and pneumonia caused by bacterial infection (0-1%).

According to the authors, 65-71% of patients had an adverse event in BORA, which led to treatment discontinuation in 2-3% of patients. In the previous studies of benralizumab SIROCCO and CALIMA, 71-75% of patients treated with benralizumab had an adverse event, with 2% discontinuing as a result of the event. Serious adverse events were reported by 10-11% of patients in BORA compared with 9-13% of patients treated with benralizumab in SIROCCO or CALIMA.

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Overall, 1-2% of patients experienced serious adverse events associated with infections during BORA, which was similar to the percentages seen previously in SIROCCO and CALIMA. According to investigators, this finding is consistent with previous reports indicating that patients with low blood eosinophil counts due to disease or treatments do not have an apparent increased risk of infections, and that eosinophil depletion by benralizumab does not increase the risk of infection. Additionally, peripheral blood eosinophil counts recovered after discontinuation of benralizumab, indicating that its effects on eosinophil depletion are not associated with long-term bone marrow suppression after medication withdrawal.

BORA, SIROCCO and CALIMA Trials

“There is an unmet medical need for effective treatments for patients with severe, uncontrolled asthma that have safety and tolerability profiles that allow their long-term use,” wrote the study’s authors, led by William Busse, MD, professor of medicine, Division of Allergy, Pulmonary and Critical Care Medicine, at the University of Wisconsin School of Medicine and Public Health. “Our findings demonstrate that long-term use of benralizumab can improve outcomes for patients with severe asthma, with an acceptable safety profile. These results should reassure respiratory care physicians of the long-term safety and efficacy of benralizumab for the treatment of asthma.”The BORA study was a randomized, double-blind, parallel-group, phase 3 extension study conducted at 447 sites in 24 countries. Between November 2014 and July 2016, investigators enrolled 1926 patients, of whom 633 had received benralizumab Q4W and 639 had received Q8W in SIROCCO or CALIMA. The remaining 654 patients had received placebo in those trials and were randomly re-assigned in the BORA trial to receive Q4W (n=320) or Q8W (n=334).

Eligible patients must have completed the SIROCCO or CALIMA trials, which investigated the effect of benralizumab 30 mg every 4 weeks (Q4W) or Q8W compared with placebo on the annual rate of exacerbations in patients aged 12-75 years with severe, uncontrolled asthma.

SIROCCO and CALIMA studies demonstrated that benralizumab combined with high-dosage inhaled corticosteroids and long-acting β₂-agonists significantly reduced asthma exacerbations and improved lung function and disease control in patients with blood eosinophil counts of 300 cells per μL or greater at baseline. For patients who received the therapy 30 mg Q8W, the annual exacerbation rate was reduced by 51% in the SIROCCO trial and 28% in the CALIMA trial compared with placebo.

“The results of this study support the use of benralizumab for the add-on maintenance treatment of patients with severe asthma with an eosinophilic phenotype not controlled with inhaled corticosteroids and long-acting β₂-agonists,” investigators concluded.