AstraZeneca is very encouraged about the prospects for benralizumab as a treatment for chronic obstructive pulmonary disease despite the investigational monoclonal antibody failing to meet its primary endpoint in a Phase IIa trial.
The study, published in The Lancet and presented at the European Respiratory Society congress in Munich, was conducted by AstraZeneca’s biologics R&D arm MedImmune. It evaluated benralizumab in 101 adults with moderate-to-severe COPD and experiencing at least one acute exacerbation requiring oral corticosteroids, antibiotics or hospitalisation in the past year.
Patients were selected on the basis of elevated levels of eosinophils, a type of white blood cell, in sputum. The primary goal of the study was not met, as benralizumab did not reduce the acute exacerbation rate compared with placebo in the overall patient population.
There was a higher incidence of serious treatment-emergent adverse events in the benralizumab group compared with placebo (14 vs 9) although none of these events were considered by the investigator to be benralizumab related. On the positive side, the drug, which targets the interleukin-5 pathway, did demonstrate clinically significant improvements in lung function in the overall population.
However AstraZeneca’s enthusiasm is primarily based on results from pre-specified analyses which showed numerical, albeit non-significant, improvement in acute exacerbations, forced expiratory volume in one second (FEV1) and overall health as measured by the St George’s Respiratory Questionnaire in benralizumab-treated patients with baseline blood eosinophil concentrations of 200-300 cells per microliter or more.
Eosinophilic airway inflammation is believed to be present in 20-30% of the 210 million people who suffer from COPD worldwide. The fact that benralizumab works best on those with the highest levels of eosinophils is consistent with the firm’s hypothesis about the drug, Bing Yao, head of MedImmune’s respiratory, inflammation and autoimmunity operations, told Pharma Times.
He noted that benralizumab is the first biologic to show marked reduction in eosinophilic inflammation and the results justify the Phase III programme for the drug in COPD which started recruiting in July. Dr Yao said the firm has now identified the patients who will benefit most from the drug on top of standard care, namely those who are uncontrolled”.
He told PharmaTimes that COPD is a heterogeneous disease and the company is advancing in its efforts to identify biomarkers and tailor therapies for patients with the disease. Personalised medicine in this area is the way forward, he added.
