MANDALA trial results showfixed dose combination of albuterol and budesonide was more effective than albuterol alone as rescue medication.
The FDA has accepted a New Drug Application (NDA) filed by AstraZeneca and British drug maker Avillion for their potential first-in-class combination short-acting beta2-agonist (SABA) and corticosteroid inhaler. PT027 combines albuterol and budesonide in a fixed-dose inhaler with a proposed indication of as-needed treatment or prevention of bronchoconstriction and prevention of exacerbations in adults and children ages 4 years and older with asthma.
The NDA submission was based on results from the MANDALA phase 3 trial. The trial enrolled participants ages 4 years and older with uncontrolled moderate-to-severe asthma who had had at least one severe asthma exacerbation in the previous 12 months. Patients ages 12 years and older were randomized to receive a combination of 180 mcg of albuterol and 160 mcg of budesonide, 180 mcg of albuterol and 80 mcg of budesonide, or 180 mcg of albuterol alone. Children ages 4 to 11 years were randomly assigned to receive the albuterol 180 mcg and budesonide 80 mcg combination or albuterol 80 mcg alone. The participants used the trial medication as needed for asthma symptoms (rescue) and before exercise as well as their regularly prescribed maintenance inhaled corticosteroid.
Patients in the higher-dose PT027 group had a 26% lower risk of severe asthma exacerbation than those taking albuterol alone. Patients using the combination inhaler also had a 33% reduction in mean annualized total dose of systemic corticosteroid. The lower-dose PT027 lowered the risk of severe asthma exacerbation in children ages 4 to 11 years by 17% more compared with albuterol.
Adverse events were similar in all treatment groups, and the most common were headache, nasopharyngitis, and upper respiratory tract infection.
Results from the MANDALA trial were published in June 2022 in the New England Journal of Medicine and presented at the American Thoracic Society 2022 International Conference in May.
In developing PT027, AstraZeneca and Avillion recognized that the conventional use of SABAs alone for asthma rescue therapy leaves patients at increased risk of severe asthma exacerbations due to unaddressed inflammation. The combination of budesonide and albuterol manages bronchoconstriction and reduces the risk of severe asthma exacerbation.
If approved, PT027 would become the first combination SABA and corticosteroid inhaler for rescue use in patients with moderate-to-severe asthma. The product would provide a steroid-containing rescue therapy that would allow patients to use their usually prescribed inhaled corticosteroid inhalers solely for maintenance therapy.