AIRSUPRA® Reduces Asthma Exacerbations in ATS 2026 Data

Asthma management guidelines have long emphasized the role of inhaled corticosteroids (ICS) for maintenance therapy and SABAs for symptom relief. However, reliance on SABA monotherapy for rescue has been associated with increased risk of severe exacerbations and adverse outcomes.¹ The rationale for combining a SABA with an ICS in a single rescue inhaler is to address both bronchoconstriction and underlying airway inflammation during acute episodes. This approach aims to provide immediate symptom relief while simultaneously delivering anti-inflammatory treatment, potentially mitigating the progression of an exacerbation.²

Asthma affects millions globally, with varying degrees of severity and significant healthcare burden due to exacerbations. These acute worsening episodes often require emergency department visits or hospitalization, impacting patient quality of life and increasing costs. Current guidelines recommend a stepwise approach to asthma management, with ICS as the cornerstone of controller therapy. Despite these recommendations, many patients continue to experience exacerbations, highlighting an unmet need for more effective rescue strategies. The development of anti-inflammatory reliever therapies (AIRT) represents a shift from traditional SABA-only rescue, aiming to provide both rapid bronchodilation and anti-inflammatory effects at the point of symptom onset. This strategy is particularly relevant given evidence that even mild asthma can be associated with airway inflammation.¹

Study Design and Findings

The clinical program for AIRSUPRA® (albuterol 90 mcg/budesonide 80 mcg) included two pivotal Phase 3 trials, MANDALA and DENALI, which evaluated its efficacy and safety in patients with moderate to severe asthma.³ The MANDALA trial was a randomized, double-blind, parallel-group, event-driven study that compared AIRSUPRA® to albuterol monotherapy in patients aged 12 years and older who were receiving maintenance ICS with or without a long-acting beta-agonist (LABA).³ The primary endpoint was the time to first severe asthma exacerbation.³

The MANDALA trial enrolled 3,132 patients across 295 sites globally.³ Patients were randomized to receive either AIRSUPRA® (albuterol 90 mcg/budesonide 80 mcg) or albuterol 90 mcg as needed for asthma symptoms.³ Over a median follow-up of 51 weeks, AIRSUPRA® demonstrated a statistically significant reduction in the risk of severe asthma exacerbations.³ Specifically, AIRSUPRA® reduced the risk of a severe asthma exacerbation by 27% compared to albuterol monotherapy (Hazard Ratio (HR) 0.73, 95% Confidence Interval (CI) 0.65-0.82, p<0.001).³ This reduction was consistent across various subgroups, including those on different background maintenance therapies.³ The trial's event-driven design ensured sufficient power to detect a difference in exacerbation rates, reflecting a real-world clinical outcome of high importance. The patient population included individuals with a history of asthma exacerbations in the year prior to enrollment, indicating a cohort at higher risk for future events.

The DENALI trial, a 12-week randomized, double-blind, parallel-group study, focused on lung function and safety.⁴ It enrolled 1,001 patients aged 12 years and older with mild to moderate asthma.⁴ DENALI showed that AIRSUPRA® provided superior improvement in forced expiratory volume in 1 second (FEV1) compared to albuterol alone and budesonide alone, 15 minutes post-dose.⁴ The mean change from baseline in FEV1 at 15 minutes post-dose was 0.28 L for AIRSUPRA® versus 0.13 L for albuterol alone (difference 0.15 L, 95% CI 0.11-0.19 L, p<0.001).⁴ The safety profile of AIRSUPRA® was generally consistent with its individual components, with common adverse events including headache and nasopharyngitis.^3,4 No new safety signals were identified.^3,4 The inclusion of a budesonide-alone arm in DENALI helped to isolate the contribution of the ICS component to the observed lung function improvements, demonstrating the synergistic effect of the combination.

These findings suggest that the inclusion of budesonide in a rescue inhaler provides a clinically meaningful benefit in reducing severe asthma exacerbations, beyond the bronchodilatory effects of albuterol alone. The data supports the concept of anti-inflammatory reliever therapy as a strategy to improve asthma control and reduce exacerbation frequency. The trials did not report on long-term effects beyond the study durations, nor did they directly compare AIRSUPRA® to other combination maintenance and reliever therapies (SMART regimens). Future research could explore these comparative effectiveness questions and the impact on overall healthcare resource utilization. While the studies demonstrated efficacy in diverse populations, the generalizability to patients with very severe or brittle asthma, or those with specific comorbidities, requires further investigation. The mechanism of action involves albuterol's rapid bronchodilation through beta-2 adrenergic receptor agonism and budesonide's anti-inflammatory effects via corticosteroid receptor binding, reducing airway hyperresponsiveness and inflammation. The co-delivery of these agents during symptomatic periods offers a targeted approach to managing acute asthma episodes.