Data from the DENALI study (NCT03847896) show that both albuterol (Ventolin HFA; GSK) and budesonide (Pulmicort Flexhaler; AstraZeneca Pharmaceuticals LP) contribute to the lung function benefits of the albuterol-budesonide (Airsupra; AstraZeneca) combination in patients with mild-to-moderate asthma, meeting the FDA’s combination rule. The treatment was well-tolerated at regular, high daily doses for 12 weeks.1
Albuterol-budesonide is a first-in-class short-acting beta-agonist/inhaled corticosteroid rescue treatment approved by the FDA for the treatment or prevention of asthma-related symptoms and to prevent sudden severe breathing problems (eg, asthma attacks or exacerbations) in patients ages 18 years and older. The decision was based on outcomes from the phase 3 MANDALA (NCT03769090) and DENALI trials, where the fixed-dose combination comprised of albuterol and budesonide led to meaningful improvements in lung function.2,3
Researchers conducted DENALI, a phase 3, randomized, double-blind, multicenter trial to fulfill the requirements of the FDA combination rule (21 CFR 300.50), which requires evidence that each component of a combination product contributes to its efficacy. They posed the hypothesis that each of the monocomponents in the combination individually contributes to lung function efficacy in patients with mild-to-moderate asthma.4
DENALI took place across 126 sites in the United States, Europe, and South America between March 2019 and July 2021. The trial enrolled 1,001 patients ages 12 and older with mild-to-moderate asthma who were randomized 1:1:1:1:1 to 4-times-daily albuterol-budesonide 180/160 μg or 180/80 μg, albuterol 180 μg, budesonide 160 μg, or placebo for 12 weeks. The trial consisted of 3 parts: a 2- to 4-week run-in period, a 12-week randomized treatment period, and a 2-week safety follow-up.4
Over the 12-week treatment period, patients receiving albuterol-budesonide 180/160 μg experienced a significantly greater improvement in lung function, measured by change from baseline in FEV₁ AUC₀–₆h, compared with those receiving budesonide 160 μg alone (least-squares mean [LSM] difference, 80.7 mL; 95% CI, 28.4–132.9; P = .003).4
At week 12, trough FEV₁—a measure of sustained lung function between doses—was also higher in patients treated with albuterol-budesonide 180/160 μg and 180/80 μg compared with those receiving albuterol 180 μg alone (LSM differences of 132.8 mL [95% CI, 63.6–201.9] and 120.8 mL [95% CI, 51.5–190.1], respectively; both P < .001).4
On day 1, the time to onset and duration of bronchodilation with albuterol-budesonide were comparable to albuterol alone, indicating that the combination maintains the rapid relief expected from albuterol.4
The researchers reported a favorable safety profile. Adverse effects (AEs) were reported by 31% to 35% of patients across the treatment groups, the most common being nasopharyngitis and headache. Thirteen patients experienced serious AEs, with one considered treatment related (an asthma exacerbation in the albuterol-budesonide 180/80 μg group). There were no deaths in the trial and less than 2% of patients discontinued treatment due to AEs.4
Local AEs typically associated with inhaled corticosteroid use occurred in 2% of patients receiving budesonide-containing treatments. These events included dysphonia (reported in 2.0%, 0.5%, and 1.0% of patients in the albuterol-budesonide 180/160 μg, albuterol-budesonide 180/80 μg, and budesonide groups, respectively), oral candidiasis (0.5%, 0.5%, and 0%), and oropharyngeal candidiasis (1.0%, 0%, and 0%, respectively).4
“The DENALI trial met both dual-primary end points, demonstrating the contribution of both monocomponents to the lung function efficacy of albuterol-budesonide pMDI,” the authors wrote. “In addition, albuterol-budesonide demonstrated a similar rapid time to onset and duration of bronchodilation on day 1 to that of albuterol.”