Fixed-dose albuterol/budesonide improves lung function, reduces asthma exacerbation risk
A fixed-dose combination of albuterol and budesonide at 180/160 µg and 180/80 µg demonstrated significant benefits in patients with asthma, according to high-level results from the MANDALA and DENALI phase 3 trials.
The trials assessed PT027 (AstraZeneca/Avillion), a fixed-dose combination of the short-acting beta agonist albuterol and the inhaled corticosteroid budesonide in a single inhaler, in adults and children aged 4 years and older with asthma, according to a company press release.
The MANDALA trial met the primary endpoint, with PT027 demonstrating significant and clinically meaningful reductions in the risk for severe exacerbations compared with albuterol, according to the release.
The randomized, double-blind, multicenter, parallel-group, event-drive phase 3 MANDALA trial evaluated the safety and efficacy of PT027 compared with albuterol alone on time to first severe exacerbation in 3,132 adults and children with moderate to severe asthma. All patients were taking maintenance inhaled corticosteroids alone or combined with other controller medications, including long-acting beta agonists, leukotriene receptor antagonists, long-acting muscarinic antagonists or theophylline, according to the release.
Patients were randomly assigned to PT027 180/160 µg (excluding those aged 11 years or younger), PT027 180/80 µg or albuterol 180 µg as a rescue medicine.
The DENALI trial met its dual primary endpoints, with PT027 demonstrating a significant improvement in lung function measured by FEV1 compared with the individual components albuterol and budesonide and compared with placebo, according to the release.
The randomized, double-blind, placebo-controlled, multicenter, parallel-group phase 3 DENALI trial evaluated safety and efficacy of PT027 vs. albuterol and budesonide alone on improvement in lung function in 1,001 adults and children with mild to moderate asthma. All patients were previously treated with SABAs as needed alone or in addition to regular low-dose inhaled corticosteroid maintenance therapy.
Patients were randomly assigned to PT027 at 180/160 µg (excluding those aged 11 years or younger), PT027 at 180/80 µg, albuterol at 180 µg, budesonide 160 µg or placebo, all four times daily. The dual primary efficacy endpoints were change from baseline in FEV1 area under the curve 0-6 hours over 12 weeks compared with budesonide and change from baseline in trough FEV1 at 12 weeks compared with albuterol, according to the release.
In both trials, safety and tolerability of PT027 were consistent with the known profiles of the components, according to the release.
“The MANDALA and DENALI trials demonstrate an albuterol/budesonide rescue inhaler can address inflammation and prevent exacerbations, making PT027 an important potential new treatment option for patients,” Bradley E. Chipps, MD, past president of the American College of Allergy, Asthma and Immunology and medical director of Capital Allergy and Respiratory Disease Center in Sacramento, California, said in the release.
“All patients with asthma are at risk of severe exacerbations, regardless of their disease severity, and many are known to overuse short-acting bronchodilators,” Mene Pangalos, AstraZeneca executive vice president of biopharmaceuticals R&D, said in the release. “These exciting results with PT027 bring us one step closer to providing an innovative and superior treatment approach for asthma by preventing exacerbations.”
Detailed data from the MANDALA and DENALI trials will be presented at an upcoming medical meeting, according to the release.