AstraZeneca posted some mixed — though generally positive — data from two big Phase III studies of benralizumab, its IL-5 contender in the highly competitive market for severe asthma. A high placebo response seriously eroded one set of late-stage data. But the therapy appears headed to an approval — even as Roche was practically given the kiss of death for a rival late-stage drug.
AstraZeneca put benralizumab through two Phase III studies that collectively recruited more than 2,500 patients. In the first of those, the CALIMA trial with 1,306 patients, 30 mg of benralizumab injected every 4 and 8 weeks was able to reduce exacerbation by 28% to 36% compared to a placebo. In the second study, SIROCCO with 1,209 patients, the exacerbation rate dropped by a more competitive 48% to 51%.
AstraZeneca’s benralizumab targets the IL-5 receptor rather than the molecule itself, a distinction that the pharma giant believes will help it compete against the recently approved Nucala (GlaxoSmithKline’s mepolizumab) and Cinqair (Teva’s reslizumab). The jury is still out on that score, though.
Nucala was approved on its ability to reduce exacerbations in asthma by tackling eosonophils, a prime biomarker for risk in the targeted population. But GSK did not prove that the drug improved lung function, while AstraZeneca’s team claims they did track amped up lung performance.
Professor Eugene Bleecker from the Center for Genomics and Personalized Medicine, Wake Forest School of Medicine, and lead author of the SIROCCO trial, had this to say:
Two drugs are currently approved for the treatment of severe, uncontrolled asthma (mepolizumab and reslizumab) but both target the IL-5 molecule directly, rather than the receptor. By targeting the IL-5 receptor, benralizumab depletes eosinophils directly, and our studies show that eosinophil counts were nearly completely depleted by week 4 of treatment.
The results were published in The Lancet Respiratory Medicine, which also concluded that Roche’s two Phase III studies for lebrikizumab fell far short of the bar on efficacy. A summary condemns the drug with slight criticism:
The findings suggest that the drug, which blocks IL-13, may not be sufficient to provide clinically meaningful improvements in reducing asthma exacerbations.
Roche concluded back in February that it had one success and one flop in Phase III, which amounts to a severe setback on this highly competitive front.
There’s also plenty of competition ahead for all the remaining players. Regeneron and Sanofi are in a Phase III asthma program for dupilumab, a potential IL-4/IL-13 megablockuster headed for a likely approval for use against atopic dermatitis. And Novartis recently touted mid-stage data on another eosinophilic drug, fevipiprant,which is designed as an oral drug that could conquer the whole market through an easier route of administration than these first-gen drugs.
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