Asthma affects about 315 million people worldwide. Among them, five to ten percent have a severe form of the disease which is treated with high-dose inhaled glucocorticoids and bronchodilators and 32 to 45 percent rely on frequent or maintenance use of oral corticosteroids.
A new study found patients with severe asthma treated with benralizumab, a potential new medicine, were more than four times likely to reduce their usage of oral corticosteroids than those taking a placebo.
Benralizumab, a monoclonal antibody against the interleukin-5 receptor, was developed by MedImmune, AstraZeneca’s global biologics research and development arm. The London-based company presented data from its Phase 3 ZONDA trial at the American Thoracic Society (ATS) 2017 International Congress.
The study was simultaneously published in The New England Journal of Medicine.
The ZONDA trial
The Phase 3 ZONDA trial evaluated the effect of benralizumab in 220 adult patients with severe uncontrolled asthma requiring treatment with a high-dose inhaled corticosteroid and long-acting beta2 agonist (LABA). The participants were randomized to receive 30 mg benralizumab subcutaneously on either an eight- or four-week dosing regimen or placebo for 28 weeks.
All the patients had been treated continuously with oral glucocorticoids for six months or more before enrollment and were receiving oral prednisone or prednisolone at trial entry. (Patients receiving any other oral glucocorticoid were switched to an equivalent dose of oral prednisone or prednisolone.) During the run-in phase of the trial, the oral glucocorticoid dose was adjusted to the minimum dose that could be received without loss of asthma control. During weeks four through 24, the doses were reduced by 2.5 to 5.0 mg/d every four weeks.
Patients continued their prescribed high-dose inhaled glucocorticoid and LABA therapies, as well as any other asthma-controller medications aside from oral glucocorticoid therapy (including leukotriene modifiers, long-acting muscarinic antagonists, and theophylline), in an unchanged fashion throughout the trial. Short-acting β2-agonists were permitted as rescue medications.
The findings showed a reduction in steroid usage while maintaining asthma control. The median reduction in oral corticosteroid dose was 75% for patients treated with benralizumab versus 25% with placebo.
“The data is very impressive,” said Parameswaran Nair, M.D., Ph.D., the study’s lead investigator, professor of medicine at McMaster University in Hamilton, Ontario and staff respirologist at St. Joseph’s Healthcare Hamilton.
“In the trial, patients were able to reduce their prednisone dose by as much as 75 percent, yet they had 70 percent less exacerbations and 93 percent less emergency room visits or hospitalizations, while maintaining their lung function,” said Nair.
In addition, the drug demonstrated significant outcomes for secondary endpoints. In the 8-week dosing regimen, 66 percent of benralizumab-treated patients reduced oral glucocorticoid doses by more than 50 percent compared with 37 percent receiving placebo; 37 percent of benralizumab-treated patients reduced oral glucocorticoid doses by more than 90 percent compared with 12 percent receiving placebo; and 52 percent of benralizumab-treated patients who were eligible to discontinue oral glucocorticoid per the trial protocol were able to stop oral glucocorticoid use completely, compared with 19 percent receiving placebo
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 observed in ZONDA were nasopharyngitis, worsening asthma and bronchitis.
The data from the ZONDA trial, along with the 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., E.U., Japan and several other countries with a U.S. FDA action date during the fourth quarter of 2017.
Filed Under: Drug Discovery