What is the mechanism of action of benralizumab and dupilumab, and when are they indicated for the treatment of asthma?

Updated: Jan 07, 2019
  • Author: Michael J Morris, MD, FACP, FCCP; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
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Answer

Benralizumab

Benralizumab is an IL-5 receptor, alpha-directed cytolytic mAb (IgG1, kappa) approved by the FDA in November 2017. The IL-5 receptor is expressed on the surface of eosinophils and basophils. Benralizumab reduces eosinophils and basophils through antibody-dependent cell-mediated cytotoxicity (ADCC). It is indicated for add-on maintenance treatment of severe asthma in patients aged 12 years or older who have an eosinophilic phenotype.

Approval was based on results from the WINDWARD clinical trial program, including the phase III exacerbation trials, SIROCCO and CALIMA, and the phase III oral corticosteroid (OCS)–sparing trial, ZONDA. [88, 89, 90]

Results for the 8-week benralizumab dosing regimen from these trials showed the following:

  • Up to 51% reduction in the annual asthma exacerbation rate (AAER) compared with placebo
  • Significant improvement in lung function as measured by forced expiratory volume in one second (FEV 1) of up to 159 mL compared with placebo
  • Seventy-five percent median reduction in daily OCS use and discontinuation of OCS use in 52% of eligible patients

Dupilumab

Approval for dupilumab was based on the LIBERTY QUEST (n=1902) and VENTURE (n=210) phase 3 clinical trials.

In the LIBERTY QUEST trial, patients with moderate-to-severe uncontrolled asthma were administered dupilumab add-on therapy to current maintenance therapy every 2 weeks or matched placebo. Those receiving a 200-mg dose demonstrated a 47.7% lower rate of annualized severe asthma exacerbations compared with placebo add-on (P<.001). The 300-mg dose showed a similar response. [91]

In the LIBERTY VENTURE trial, patients with oral corticosteroid–dependent severe asthma were administered dupilumab add-on therapy or matched placebo to current maintenance therapy every 2 weeks for 24 weeks or matched placebo. Corticosteroid doses were gradually decreased from week 4 to week 20 and then maintained for 4 weeks. Patients receiving dupilumab had a 70.1% greater corticosteroid dose reduction compared with 41.9% for placebo add-on (P<.001). Additionally, patients receiving dupilumab had a 59% (95% confidence interval, 37-74) lower rate of severe asthma exacerbations than those taking placebo add-on. [92]


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