Meeting News

Two-year analysis demonstrates long-term safety, efficacy of benralizumab in severe asthma

DALLAS — In patients with severe asthma treated with benralizumab, reduced exacerbation rates and improved pulmonary function, asthma control and health-related quality of life were maintained without any unexpected safety findings at 2 years, according to an analysis presented at the American Thoracic Society International Conference.

Benralizumab (Fasenra, AstraZeneca) showed benefit in patients with severe, uncontrolled eosinophilic asthma in the 48-week SIROCCO and 56-week CALIMA trials, as well as in the oral corticosteroid-sparing 28-week ZONDA trial. After completion of these trials, patients could continue in the ongoing, long-term safety and efficacy 1-year BORA study.

“The anti-eosinophilic treatments are relatively new, so there’s a lot of interest from a regulatory point of view, for prescribing suggestions and also from patients about their safety,” J. Mark FitzGerald, MD, professor of respiratory medicine at the University of British Columbia in Canada, told Healio Pulmonology. “The regulatory trials to approve these drugs are relatively short, so the main purpose of this study was to see if the drugs continue to be effective and safe and that we don’t identify any unexpected adverse events or side effects.”

Continued safety, efficacy

For this study, FitzGerald and colleagues analyzed 2-year integrated safety and efficacy data for patients in SIROCCO and CALIMA who continued in BORA. At the beginning of the study, patients received medium- or high-dose inhaled corticosteroids or long-acting beta-agonists. They then received benralizumab 30 mg every 4 weeks or every 8 weeks. The ZONDA trial patients were analyzed separately, as it had a different trial design.

The integrated analysis included 1,161 patients treated with benralizumab — 1,030 in the SIROCCO, CALIMA and BORA full analysis set and 131 in the ZONDA and BORA analysis set.

During the integrated period, both patients who received benralizumab every 4 weeks and those who received benralizumab every 8 weeks were exposed to the treatment for an average of about 2 years. The integrated analysis showed that improvements in exacerbation rate, forced expiratory volume in 1 second, Asthma Control Questionnaire-6 scores and Asthma Quality of Life Questionnaire observed at 1 year were maintained through 2 years of treatment.

In the integrated analysis of ZONDA and BORA, three-quarters of patients had at least a 50% reduction in their dose of oral corticosteroids from baseline after 84 weeks of treatment every 8 weeks and 39% had an at least 90% reduction. There was also a 65% reduction in oral corticosteroid dosage by the end of the integrated study period, which was comparable to reductions seen in the ZONDA trial.

Similarly, there was no increase in the frequencies of overall or serious adverse events, with the most common adverse events being viral upper respiratory infection, upper respiratory tract infection and bronchitis.

Answered questions

This study, FitzGerald noted, puts some of the concerns about benralizumab to rest.

“Benralizumab is particularly effective at reducing eosinophils and some people have been concerned that the treatment might be associated with an increased risk for infections, but this analysis shows that is not the case,” he said. “Because this entire class of drugs affect the immune system to some extent, there is always concern that they can cause problems in terms of cancer malignancy and, again, there were no unexpected patterns or trends showing that to be an issue. Finally, some people develop an antibody that blocks the drug, which is a problem with all the monoclonal antibodies. With benralizumab, though, the rate has remained consistent — around 5% — and it hasn’t increased over time. Also, among people who develop these antibodies, it didn’t appear to affect the benefits they got form the treatment.”

As for future research, FitzGerald and colleagues hope to gather more data that will help identify which patients will benefit most from this treatment.

“The more information we can get in terms of predicting the ideal patient who responds best to this treatment, the better,” he told Healio Pulmonology. “Any features that we can identify would allow us to treat patients more effectively. Soon, we’re probably going to have more drugs in this class as well as other classes available to us and identifying the best patient in terms of how you use these drugs will be a very important area of research.” – by Melissa Foster

Reference:

FitzGerald JM. Abstract 2676. Presented at: American Thoracic Society International Conference; May 17-22, 2019; Dallas.

Disclosure: FitzGerald reports he is the principal investigator for the CALIMA and SIROCCA studies; he has been involved with the benralizumab drug development program; and he is a member of the speakers’ bureau for AstraZeneca.

DALLAS — In patients with severe asthma treated with benralizumab, reduced exacerbation rates and improved pulmonary function, asthma control and health-related quality of life were maintained without any unexpected safety findings at 2 years, according to an analysis presented at the American Thoracic Society International Conference.

Benralizumab (Fasenra, AstraZeneca) showed benefit in patients with severe, uncontrolled eosinophilic asthma in the 48-week SIROCCO and 56-week CALIMA trials, as well as in the oral corticosteroid-sparing 28-week ZONDA trial. After completion of these trials, patients could continue in the ongoing, long-term safety and efficacy 1-year BORA study.

“The anti-eosinophilic treatments are relatively new, so there’s a lot of interest from a regulatory point of view, for prescribing suggestions and also from patients about their safety,” J. Mark FitzGerald, MD, professor of respiratory medicine at the University of British Columbia in Canada, told Healio Pulmonology. “The regulatory trials to approve these drugs are relatively short, so the main purpose of this study was to see if the drugs continue to be effective and safe and that we don’t identify any unexpected adverse events or side effects.”

Continued safety, efficacy

For this study, FitzGerald and colleagues analyzed 2-year integrated safety and efficacy data for patients in SIROCCO and CALIMA who continued in BORA. At the beginning of the study, patients received medium- or high-dose inhaled corticosteroids or long-acting beta-agonists. They then received benralizumab 30 mg every 4 weeks or every 8 weeks. The ZONDA trial patients were analyzed separately, as it had a different trial design.

The integrated analysis included 1,161 patients treated with benralizumab — 1,030 in the SIROCCO, CALIMA and BORA full analysis set and 131 in the ZONDA and BORA analysis set.

During the integrated period, both patients who received benralizumab every 4 weeks and those who received benralizumab every 8 weeks were exposed to the treatment for an average of about 2 years. The integrated analysis showed that improvements in exacerbation rate, forced expiratory volume in 1 second, Asthma Control Questionnaire-6 scores and Asthma Quality of Life Questionnaire observed at 1 year were maintained through 2 years of treatment.

In the integrated analysis of ZONDA and BORA, three-quarters of patients had at least a 50% reduction in their dose of oral corticosteroids from baseline after 84 weeks of treatment every 8 weeks and 39% had an at least 90% reduction. There was also a 65% reduction in oral corticosteroid dosage by the end of the integrated study period, which was comparable to reductions seen in the ZONDA trial.

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Similarly, there was no increase in the frequencies of overall or serious adverse events, with the most common adverse events being viral upper respiratory infection, upper respiratory tract infection and bronchitis.

Answered questions

This study, FitzGerald noted, puts some of the concerns about benralizumab to rest.

“Benralizumab is particularly effective at reducing eosinophils and some people have been concerned that the treatment might be associated with an increased risk for infections, but this analysis shows that is not the case,” he said. “Because this entire class of drugs affect the immune system to some extent, there is always concern that they can cause problems in terms of cancer malignancy and, again, there were no unexpected patterns or trends showing that to be an issue. Finally, some people develop an antibody that blocks the drug, which is a problem with all the monoclonal antibodies. With benralizumab, though, the rate has remained consistent — around 5% — and it hasn’t increased over time. Also, among people who develop these antibodies, it didn’t appear to affect the benefits they got form the treatment.”

As for future research, FitzGerald and colleagues hope to gather more data that will help identify which patients will benefit most from this treatment.

“The more information we can get in terms of predicting the ideal patient who responds best to this treatment, the better,” he told Healio Pulmonology. “Any features that we can identify would allow us to treat patients more effectively. Soon, we’re probably going to have more drugs in this class as well as other classes available to us and identifying the best patient in terms of how you use these drugs will be a very important area of research.” – by Melissa Foster

Reference:

FitzGerald JM. Abstract 2676. Presented at: American Thoracic Society International Conference; May 17-22, 2019; Dallas.

Disclosure: FitzGerald reports he is the principal investigator for the CALIMA and SIROCCA studies; he has been involved with the benralizumab drug development program; and he is a member of the speakers’ bureau for AstraZeneca.

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