Benralizumab: a novel anti-eosinophil monoclonal antibody

Science and the millions of patients with severe, uncontrolled asthma with an eosinophilic phenotype have much to consider this week as we reveal important pivotal phase 3 study data about benralizumab at this year’s European Respiratory Society (ERS) International Congress held in London.

Benralizumab is a monoclonal antibody (mAb) that depletes eosinophils via antibody-dependent cell-mediated cytotoxicity, the process by which natural killer cells are activated to target eosinophils. Today, we know that eosinophils are important drivers of frequent exacerbations of patients with asthma, and particularly those with severe, uncontrolled asthma.

Beyond an IL-5 inhibitor
When we completed our first phase 1 trial of benralizumab in 2008, however, it was unmistakable: We were on to something very important. In that trial, we discovered a potent, rapid and sustained depletion of eosinophils. Within 24 hours after the first dose was administered to patients, eosinophils were no longer detectable. In a subsequent clinical study, we also saw a >95% reduction of eosinophils in lung tissue and complete depletion in the bone marrow, the tissue site where eosinophils originate.

The data revealed that benralizumab was taking a direct path to eosinophils and wiping them out.

Novel drug, different mechanism of action
For patients in our clinical trials, data showed a reduction in annual exacerbations and improvement in lung function and asthma symptoms —with adverse event frequency similar between benralizumab and placebo-treated patients in both pivotal studies and few frequent adverse events, and infrequent dose (every 8 weeks). Benralizumab binds directly to the eosinophil via the IL-5 receptor on the surface of the cell and induces direct, rapid, and near complete depletion of eosinophils in the bone marrow, blood and target tissue.

Today, as we release this pivotal phase 3 trial data for our first respiratory biologic, for those of us who have been working on benralizumab for the past decade, it is a bit like watching your child grow to achieve adult success—novel success. Having met primary and key secondary endpoints in these momentous trials, our hope is that we are able to offer a treatment option in meaningful ways as an add-on therapy for severe, uncontrolled asthma with eosinophilic inflammation.

As we move forward, we will be looking more closely at benralizumab for other eosinophilic diseases—COPD is something we’re already investigating, for example. There are still many unmet needs within the circumference of asthma, of course, and we are very aware of its heterogeneity. But, the eosinophilic model offers an important principle through which we continue to look toward targeting the right patients with the right drugs. Within the larger context of our RIA research and development, our focus is on the biological pathways that characterize these conditions and that may offer a platform for disruptive breakthroughs in treatment.

You can access the full phase 3 trial data for benralizumab, which has been published in The Lancet and presented today at ERS

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