GlaxoSmithKline's mepolizumab succeeded in two Phase III asthma trials, whereas AstraZeneca's benralizumab failed in a Phase II chronic obstructive pulmonary disease trial.

The lowdown: In 2000, GlaxoSmithKline (GSK) hit a wall when its interleukin-5 (IL-5)-specific antibody mepolizumab failed in its first Phase II trial. Nearly 15 years on, after a rethink on asthma trials (Nature Rev. Drug Discov. 11, 737–738; 2012) and increased insight into eosinophil function (Nature Rev. Drug Discov. 12, 117–129; 2013), the company has found a way to the other side. The drug met its primary end point in a Phase III trial in 576 patients with severe eosinophilic asthma, reducing the rate of asthmatic exacerbations by 47%–53% compared with placebo, GSK recently reported (Ortega, H. G. et al. N. Engl. J. Med. 8 Sep 2014). It also met its primary end point in a smaller 135-patient Phase III trial, reducing the daily oral glucocorticoid dose needed to effectively treat patients' symptoms (Bel, E. H. et al. N. Engl. J. Med, 8 Sep 2014).

A regulatory filing is now expected by the end of the year. Yet, a linked editorial notes that although the drug was safe and effective, “these studies do not suggest that all patients with uncontrolled asthma who have peripheral blood eosinophilia will require an expensive anti-IL-5 therapy for clinical benefit”. Parameswaran Nair, of McMaster University, Canada, points out that the exacerbation rate in the larger trial fell by over 50% even with just the placebo, which suggests that many patients may benefit just from improved adherence to available drug regimens and good clinical practice (Nair, P. N. Engl. J. Med. 8 Sep 2014).

AstraZeneca's IL-5 receptor (IL-5R)-specific benralizumab and Teva's IL-5-specific reslizumab are also in Phase III trials for asthma.

AstraZeneca and GSK have also both moved their drugs into Phase III for chronic obstructive pulmonary disease (COPD). AstraZeneca reported in September, however, that their benralizumab failed to reduce the exacerbation rate in an 82-patient Phase II trial (Lancet Respir. Med. 8 Sep 2014). “The results of prespecified subgroup analysis support further investigation of benralizumab in patients with COPD and eosinophilia,” the authors note.