AstraZeneca show positive results in phase III ZONDA trial severe asthma
Results from AstraZeneca's phase III ZONDA trial demonstrated that adding benralizumab to standard-of-care allowed patients dependent on OCS to significantly reduce or discontinue steroids while maintaining asthma control. Detailed results of the ZONDA study were published in the New England Journal of Medicine.
The trial achieved its primary efficacy endpoint, demonstrating statistically-significant and clinically relevant reduction in daily maintenance OCS use with two benralizumab dosing regimens compared with placebo. Patients treated with benralizumab were more than four times as likely to reduce their OCS dose than those in the placebo group. The median reduction in OCS dose was 75% for patients treated with benralizumab versus 25% with placebo.
The ZONDA trial demonstrated significant outcomes for secondary endpoints. For OCS reduction in the 8-week dosing regimen:
- 66% of benralizumab-treated patients reduced OCS doses by =50% compared with 37% receiving placebo
- 37% of benralizumab-treated patients reduced OCS doses by =90% compared with 12% receiving placebo
- 52% of benralizumab-treated patients who were eligible to discontinue OCS per the trial protocol were able to stop OCS use completely, compared with 19% receiving placebo
Analysis of prevention or reduction of acute asthma events in benralizumab-treated patients on the 8-week dosing regimen demonstrated:
- 70% reduction in overall annual exacerbation rate compared with placebo
- 93% reduction in exacerbations requiring emergency room visits or hospitalizations compared with placebo
Dr. Parameswaran Nair, professor of Respiratory Medicine at McMaster University in Hamilton, Canada and the lead investigator of the trial, said, “Benralizumab showed an impressive clinical efficacy by reducing exacerbations rate by up to 70% at the same time enabling patients with severe asthma to significantly lower their prednisone dose and maintain their lung function. This is likely due to its unique mechanism of action of inhibiting the receptor for interleukin-5 and potentially depleting blood and airway eosinophils.”
Sean Bohen, executive vice president, Global Medicines Development and Chief Medical Officer, said, “One of the known clinical characteristics of the eosinophilic asthma phenotype is an over reliance on oral steroids to manage severe uncontrolled disease. What is exciting about the ZONDA trial is that we have shown benralizumab delivers a clinically meaningful OCS reduction alongside a substantial reduction in asthma exacerbation rate including emergency treatment or hospitalizations in this difficult-to-treat patient population.”
The ZONDA trial evaluated the effect of benralizumab 30mg administered subcutaneously (SC) using either an 8- or 4-week dosing regimen for 28 weeks in adult patients with severe, uncontrolled eosinophilic asthma receiving high-dose inhaled corticosteroid (ICS)/long-acting beta2 agonist (LABA) and OCS with or without additional asthma controllers. Benralizumab was well-tolerated, with an overall adverse event profile like that of placebo and that observed in previous Phase III trials. The most common adverse events (=10%) in benralizumab-treated patients observed in ZONDA were nasopharyngitis, worsening asthma and bronchitis.
The data from the ZONDA trial, along with the pivotal phase III SIROCCO and CALIMA trials, were included in regulatory submissions for benralizumab. Benralizumab is not approved anywhere in the world, but is under regulatory review in the U.S., EU, Japan and several other countries with a U.S. PDUFA date in the fourth quarter of 2017.