Long-term use of benralizumab efficacious, safe for severe, uncontrolled asthma

Long-term treatment with the interleukin-5 receptor alpha-directed cytolytic monoclonal antibody benralizumab led to long-term control of asthma, improvement in pulmonary function, and was safe in patients with severe eosinophilic asthma in the 2-year integrated analysis of the SIROCCO, CALIMA, and ZONDA pivotal studies plus the BORA extension study reported at ATS 2019.

“Reduced exacerbation rates, as well as improved pulmonary function, asthma control, and health-related quality of life, were sustained through 2 years in patients in SIROCCO and CALIMA studies who progressed to BORA,” reported study investigator Dr J. Mark FitzGerald, director of the Centre for Heart and Lung Health at the Vancouver Coastal Health Research Institute.” Long-term treatment with benralizumab was well-tolerated, with no new or unexpected safety findings.” [ATS 2019, abstract 511]

FitzGerald and his team analysed data on patients initiated on benralizumab in SIROCCO and CALIMA studies and continued in BORA, and those in ZONDA who continued in BORA (≤1.5 years of benralizumab treatment). Patients received medium- or high-dose inhaled corticosteroids/long-acting β2-agonists at study initiation and benralizumab 30 mg every 4 weeks (Q4W) or every 8 weeks (Q8W, first three doses Q4W).

The SIROCCO and CALIMA full analysis set (FAS) included patients who completed SIROCCO or CALIMA, received ≥1 dose of study treatment in BORA (allowing evaluation of up to 2 years data), and did not continue into another trial. Data from patients who initiated treatment in ZONDA and transitioned into BORA (allowing evaluation of ≤1.5 years of data) were analysed separately because of trial design differences and treatment duration (28 weeks for ZONDA vs 48 and 56 weeks for SIROCCO and CALIMA, respectively).

The SIROCCO and CALIMA full analysis set for the integrated studies included 1,030 and 1,655 patients, respectively, randomized to benralizumab Q4W or Q8W. During the integrated period, mean benralizumab exposure was 24.3 and 24.6 months, respectively, for benralizumab Q4W (n=518) and Q8W (n=512) groups. Reductions in exacerbation frequency were maintained as were improvements in prebronchodilator FEV1, ACQ-6 scores, and AQLQ(S)+12 scores.

In 131 patients from ZONDA who transitioned to BORA, median daily OCS dosage was reduced from baseline with benralizumab Q8W by 75 percent at the end of the trial in ZONDA and sustained through the end of the extension period (67 percent) for patients with blood eosinophil counts ≥150 cells/μL.

Approximately 40 percent of patients had a ≥90 percent reduction from baseline in OCS use at the end of the ZONDA trial and throughout the extension period with benralizumab Q8W. Improvements in OCS reductions observed in ZONDA were maintained through BORA.

In the SIROCCO and CALIMA full analysis set and the ZONDA groups, rates of all treatment-emergent adverse events (TEAEs) and serious AEs were similar between the BORA extension and SIROCCO, CALIMA and ZONDA study periods. Risk of infection did not increase over time with benralizumab, and the malignancy rate was low.

Although potentially anticipated, long-term eosinophil depletion did not result in increased serious infection rates or helminth infections.

“Overall, the results of the integrated analysis of the SIROCCO, CALIMA, and ZONDA studies, and the BORA extension study findings, further confirm the long-term efficacy and safety of benralizumab for the treatment of patients with severe, uncontrolled asthma,” said FitzGerald. “The same results will be relevant for guiding clinical decisions on the long-term use of benralizumab.”

He added that the new evidence for benralizumab give confidence to physicians knowing that their ability to reduce their patients’ OCS use can be maintained in the long term, which is a key treatment goal given the potential for significant adverse effects.

Severe eosinophilic asthma is a debilitating chronic disease characterized by elevated levels of eosinophils in the blood. Patients with eosinophilic asthma have varying degrees of atopy, which can be nonatopic to atopic. They may have frequent exacerbations, low FEV₁ with persistent airflow limitation, allergic rhinitis, and normal or moderately elevated immunoglobulin E (IgE).

If untreated, eosinophilic asthma can lead to serious consequences, including airway smooth muscle contraction, airway hyperresponsiveness, and airway remodeling. In addition, eosinophilic inflammation can lead to progressive airway damage and poor control.

Benralizumab is approved for the add-on maintenance treatment of patients 12 years and older with severe eosinophilic asthma in many countries. Currently, it is not indicated for the treatment of other eosinophilic conditions or relief of acute bronchospasm or status asthmaticus.