Experimental Treatments: Benralizumab (MEDI-563)

Benralizumab (MEDI-563) is a subcutaneous (SC) injection therapy being developed by AstraZeneca and MedImmune.

Like mepolizumab, benralizumab is an antibody (biological drug) of Interleukin 5 (IL5), an immune system hormone. This hormone controls the production, activation, recruitment, and proliferation of eosinophils at an inflammation site.  In excess, eosinophils (a type of white blood cell) can cause inflammation in the lungs, ultimately leading to excess sputum production that causes exacerbations, or a worsening of  respiratory symptoms.

The drug is being investigated as a treatment of severe asthma and chronic obstructive pulmonary disease (COPD), both with sputum eosinophilia.

Benralizumab and clinical trials for the treatment of COPD

According to the clinicaltrials.gov website there are four studies of benralizumab as a COPD treatment.

A Phase 2a study (NCT01227278), completed in 2013, aimed to evaluate if benralizumab reduced exacerbations in people with moderate to severe COPD and sputum eosinophilia. About 421 participants (ages 40–85) enrolled in this double-blind, placebo-controlled study. They were given either SC injections of benralizumab (100 milligram) or a placebo every four weeks for the first three doses, and then every eight weeks for the next five doses. Results, published in The Lancet in September 2014, showed that it did not reduced exacerbations compared to placebo. However, the drug had a positive impact on lung function, quality of life and COPD symptoms, supporting further investigation.

Two Phase 3 studies are ongoing, NCT02138916 (known as GALATHEA) and NCT02155660 (known as TERRANOVA). Both are aimed to determine if SC injections of benralizumab reduce COPD exacerbations in people with moderate to very severe COPD that are receiving standard care therapies. In total, around 4,472 people are enrolled in these 56 weeks, randomized, double-blind, placebo controlled safety and efficacy studies, which are expected to finish in April 2018.

A Phase 1 study (NCT02968914), testing the pharmacokinetics of particular ways of administering benralizumab, is currently recruiting healthy volunteers in Germany. This randomized, open-label, and parallel group study aims to compare drug exposure  of  a single dose of benralizumab SC injection given via accessorized pre-filled syringe (APFS) or by autoinjector (AI). About 180 volunteers will be enrolled in this study, expected to end in June 2017.

Other details

It was first tested in people with mild asthma in a Phase 1 study (NCT00512486) completed in 2008. Results demonstrated the drug’s safety and raised its potential as a treatment, with the most frequent side effects reported being injection site reaction, headache, nasopharyngitis (common cold), and nausea.

The two Phase 3 studies for asthma patients with eosinophils, SIROCCO (NCT01928771) and CALIMA (NCT01914757) are part of the WINDWARD program for biologic treatment of a respiratory disease. Both studies evaluated the efficacy and safety of fixed 30 -milligram SC injections of benralizumab as an add-on therapy for people with asthma exacerbations and eosinophilic phentotype. Preliminary results showed that benralizumab significantly reduced asthma exacerbations and symptoms and improved lung function.

Benralizumb is also being studied as a potential treatment for conditions such as eosinophilic chronic rhinosinusitis or hypereosinophilic syndrome.