- AstraZeneca said Tuesday its experimental drug benralizumab significantly reduced the need for patients with severe asthma to take oral corticosteroids in a Phase 3 trial, strengthening the drug's chances of approval later this year in the U.S.
- Benralizumab would be AstraZeneca's first biologic respiratory medicine to reach markets, if approved. The British drugmaker views biologics as a driver of respiratory market growth over the next decade and has identified three compounds — including benralizumab — that it believes can make up a sector-leading biologics portfolio.
- For patients with severe asthma, oral corticosteroids are often the last remaining option to help control symptoms but cause a wide range of serious side effects. In the study, dubbed ZONDA, treatment with benralizumab resulted in a median 75% reduction from baseline in oral glucocorticoid dose, compared to an only 25% reduction for those on placebo.
Respiratory disease has long been a focus for AstraZeneca and continues to be a core area of development alongside oncology and cardiovascular and metabolic diseases.
Symbicort (budesonide/formoterol) and Pulmicort (budesonide), AstraZeneca's flagship respiratory brands, together pulled in over $4 billion in product revenue last year. With generic competition eroding sales of Crestor (rosuvastatin), the two accounted for a fifth of company revenues over the first three months of 2017.
But pricing pressures in the U.S. and new rivals in chronic obstructive pulmonary disease have weighed on Symbicort, depressing sales by 10% last year.
Benralizumab, along with the recently launched Bevespi (glycopyrrolate/formoterol fumarate), figure to be a large part of how AstraZeneca plans to offset further revenue losses from its top brand and maintain its leadership position in the therapeutic area.
ZONDA is the third late-stage study to test benralizumab. Two others, SIROCCO and CALIMA, read out positive last year, showing the monoclonal antibody added to standard of care reduced the annual rate of asthma exacerbations by as much as half compared to placebo.
Results from all three studies were included in AstraZeneca's regulatory submission for benralizumab, which has a target action date set for sometime in the fourth quarter.
Benralizumab targets a type of blood cell known as eosinophils, which are tied to the development of asthma. By inhibiting a receptor for a cytokine called interleukin-5 (IL-5), benralizumab can rapidly deplete blood and airway eosinophils. Earlier studies showed benralizumb led to depletion of circulating eosinophils within 24 hours of treatment.
But benralizumab, if approved, won't be the first eosinophil-targeting drug to make it to market. GlaxoSmithKline's Nucala (mepolizumab) and Teva's Cinqair (reslizumab) also target IL-5 to reduce the number of eosinophils.
AstraZeneca believes benralizumab's mechanism of action is differentiated, however, as it binds directly to a subunit of the IL-5 receptor.
"Direct mechanism translated into faster onset of action and comprehensive efficacy including lung function improvement, asthma control [and] exacerbation reduction," said Bing Yao, head of respiratory, inflammation & autoimmunity at MedImmune, in an interview.
MedImmune is a subsidiary of AstraZeneca and the developer of benralizumab.
Additionally, benralizumab is dosed every 8 weeks rather than monthly — a more convenient treatment regimen that could serve as a competitive advantage if the drug makes it to market.
While benralizumab's success in ZONDA gives AstraZeneca a lift in respiratory, the British drugmaker announced on Tuesday results from a separate study which could crimp growth expectations for its diabetes drug Bydureon (exenatide). The Phase 3b/4 EXSCEL trial showed Bydureon didn't increase cardiovascular risk compared to placebo — meeting the primary objective — but failed to demonstrate a heart benefit. Missing out on that efficacy objective could cede ground to Novo Nordisk in the competitive GLP-1 class of diabetes drugs.