LONDON, United Kingdom — For patients with severe uncontrolled eosinophilic asthma, the anti-interleukin (IL)-5 pathway can be targeted with the investigational biologic agent benralizumab, two phase 3 studies show.
Results from the two studies were presented here at the European Respiratory Society (ERS) International Congress 2016 and published online simultaneously in the Lancet (SIROCCO and CALIMA).
In this hard-to-treat asthma population, two other anti-IL-5 therapies — mepolizumab and reslizumab — have been shown to reduce rates of asthma exacerbation, "but both target the IL-5 molecule directly, rather than the receptor," lead SIROCCO investigator Eugene Bleecker, MD, from the Wake Forest School of Medicine in Winston–Salem, North Carolina, explained in a news release.
"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," he said.
This new mechanism of action addresses "the unmet needs of these patients," report lead CALIMA investigator Mark FitzGerald, MD, from the University of British Columbia Institute for Heart and Lung Health in Vancouver, Canada, and his colleagues.
The two studies involved patients 12 to 75 years of age who were being treated with inhaled corticosteroids and long-acting beta-agonists yet experienced at least two exacerbations in the previous year.
Patients were randomized to benralizumab 30 mg every 4 weeks or every 8 weeks or placebo.
In the SIROCCO trial, treatment duration was 48 weeks and 809 of the 1205 participants had eosinophil counts above 300 cells/µL at baseline.
In the CALIMA trial, treatment duration was 56 weeks and 728 of the 1306 participants had eosinophil counts above 300 cells/µL at baseline.
With 4-week dosing, the rate of exacerbation was 45% lower than with placebo in the SIROCCO trial and 36% lower in the CALIMA trial. With 8-week dosing, the rate of exacerbation was 51% lower than with placebo in the SIROCCO trial and 28% lower in the CALIMA trial.
In both trials, lung function and total asthma scores improved with 8-week dosing.
Table. Annual Asthma Exacerbations
| Baseline | End of Study | Rate Ratio vs Placebo | P Value | |
| SIROCCO | ||||
| Placebo | 3.10 | 1.33 | — | |
| 4-week dosing | 3.00 | 0.73 | 0.55 | <.0001 |
| 8-week dosing | 2.80 | 0.65 | 0.49 | <.0001 |
| CALIMA | ||||
| Placebo | 2.98 | 0.93 | — | |
| 4-week dosing | 2.80 | 0.60 | 0.64 | .0018 |
| 8-week dosing | 2.70 | 0.66 | 0.72 | .0188 |
In the SIROCCO trial, adverse events during the treatment period were reported by 72% of benralizumab-treated patients and 76% of placebo-treated patients. In the CALIMA trial, rates were 74% and 78%, respectively.
"The age of precision medicine has arrived for the subset of severe asthma patients with an eosinophilic-driven phenotype," Mario Castro, MD, and Leonard Bacharier, MD, from the Washington University School of Medicine in St. Louis, Missouri, write in an editorial that accompanies the published studies.
But the vast majority of asthma patients don't actually need such expensive treatment, said Peter Barnes, DM, head of respiratory medicine at Imperial College London, United Kingdom, and chair of the ERS.
Not for the Vast Majority
Although "there is a need for something for people who cannot be controlled with maximum inhaled treatment," such patients are "quite rare," he explained
The most common cause of uncontrolled asthma, by far, is that "people don't use their treatment," he told Medscape Medical News.
There are "very few people" who have high eosinophils despite maximum treatment, he pointed out. "It is probably one in 1000."
"This new treatment is going to cost €20,000 a year, or something like that, so it's really important that clinicians are checking how well their patients are using existing treatments before they start prescribing these very expensive injections," Dr Barnes said.
The studies were funded by AstraZeneca and Kyowa Hakko Kirin, manufacturers of benralizumab. Dr Bleecker and Dr FitzGerald have disclosed no relevant financial relationships.
European Respiratory Society (ERS) International Congress 2016: Abstracts OA 4832 and OA 1969. Presented September 5, 2016.
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Cite this: Injected Benralizumab Targets Eosinophils in Severe Asthma - Medscape - Sep 06, 2016.
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