AstraZeneca has hit a bump in the road for its biologic respiratory drug benralizumab after it missed its primary goal in a study involving patients with chronic obstructive pulmonary diseases (COPD).
The results of the phase IIa study revealed that the drug was unable to improve the rate of flare-ups in COPD patients compared to placebo but – on the plus side – did show that the drug achieved “clinically significant improvements in lung function,” according to AZ.
The data – which was presented at the European Respiratory Society (ERS) congress this week and also published in The Lancet – also showed that benralizumab reduced COPD exacerbations and improved other symptoms in some patient subgroups.
Benralizumab is one of a number of interleukin-5 inhibitors coming through the pipeline for indications such as severe asthma and COPD, and was tipped as a future blockbuster by AZ during its last R&D presentation, which was held in the midst of the unwanted takeover attempt by Pfizer.
The drug – along with rivals such as mepolizumab from GlaxoSmithKline (GSK) and Teva’s reslizumab – is thought to work by depleting the body of eosinophils, a type of white blood cell linked to exacerbations in asthma and also potentially COPD.
GSK reported data at the ERS that showed eosinophils in the blood can be used as a biomarker to predict patients with COPD who will experience reductions in exacerbations after treatment with inhaled corticosteroids (ICS), which have a broader impact on white cell levels but also reduce eosinophils.
The company’s head of respiratory medicine, Neil Barnes, pointed out that COPD is a heterogeneous disease and “enhancing our understanding of how individual patients respond to different treatments is critical to allow treatment to be tailored to their specific needs.”
In AZ’s phase IIa study, patients with the highest levels of eosinophils in their sputum at enrolment seemed to derive the most benefit from the drug, with grater improvements in exacerbation rate, lung function and reported health status than placebo-treated subjects.
Eosinophilic airway inflammation is believed to be present in up to 30% of the 210 million people who live with COPD worldwide, according to AZ.
Benralizumab started phase III trials in severe, uncontrolled asthma last October and was moved into late-stage testing as a COPD therapy in July. AZ has suggested it could be a $2bn product at peak if approved for both indications, and analysts have said the IL-5 inhibitor class as a whole could collectively amass sales of more than $7bn at peak.
The lead investigator in the phase IIa study, Prof Christopher Brightling of the University of Leicester in the UK, insisted the results “reinforce the further development of this molecule for COPD”, even though the primary outcome measure in the trial was missed.
AZ is certainly committed to pushing forward with benralizumab in COPD, despite the setback.
“We are working to better understand patient subtypes, identify potential biomarkers and tailor therapies to achieve the best outcomes for patients,” said Bing Yao, who heads up respiratory R&D at the company’s Medimmune biologics unit.