Data from the MANDALA and DENALI clinical trials led to the recent FDA-approval of albuterol/budesonide for the as-needed treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in people with asthma aged 18 years and older. Explore the data that led to its approval with this quick recap.
The US Food and Drug Administration (FDA) has recently approved albuterol/budesonide, formerly known as PT027, for the as-needed treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in people with asthma aged 18 years and older.
It is a combination of albuterol, a short-acting beta2-agonist (SABA), and budesonide, an anti-inflammatory inhaled corticosteroid (ICS). It is the first combination of an ICS and a SABA to be approved in the US and is given as two oral inhalations of a combination of albuterol 90 mcg and budesonide 80 mcg per inhalation (total dose of albuterol 180 mcg and budesonide 160 mcg) as needed for asthma symptoms. The treatment works to relax the muscles and reduce inflammation in the lung airways to reduce the risk of severe asthma attacks.
The FDA approval of albuterol/budesonide is based on the randomized, double-blind, multicenter, parallel-group, event-driven MANDALA and DENALI phase 3 trials.
DENALI Trial
The DENALI trial evaluated the efficacy and safety of PT027 compared to its component’s albuterol and budesonide on improvement in lung function in 1,001 adults, adolescents, and children aged 4–11 years with mild to moderate asthma previously treated either with SABA as-needed alone or in addition to regular low-dose ICS maintenance therapy. Patients were randomly assigned to one of the following five treatment groups in a 1:1:1:1:1 ratio: PT027 180/160mcg four times daily (excluding children aged 4-11 years), PT027 180/80mcg four times daily, albuterol 180mcg four times daily, budesonide 160mcg four times daily, and placebo four times daily (excluding children aged 4-11 years).
The results showed that PT027 demonstrated a statistically significant improvement in lung function compared to individual components in mild to moderate asthma. The study marks the first time an albuterol/budesonide fixed-dose combination rescue medication has been shown to improve lung function in mild to moderate asthma.
MANDALA Trial
The MANDALA Phase III trial evaluated the efficacy and safety of PT027 used as an as-needed rescue medication in patients with asthma. The trial included 3,132 patients, which included adults, adolescents, and children aged 4-11 years, with moderate to severe asthma taking maintenance ICS with or without additional controller medicines. Patients were randomly assigned to one of the following three treatment groups in a 1:1:1 ratio: PT027 180/160mcg (excluding children aged 4–11 years), PT027 180/80mcg, or albuterol 180mcg, taken as an as-needed rescue medicine.
The results showed that PT027 significantly reduced the risk of a severe exacerbation compared to albuterol alone. The lower budesonide dose (180mcg albuterol/80mcg budesonide) also demonstrated a statistically significant reduction of 17 percent in the risk of severe exacerbation versus albuterol rescue. The study marks the first time an albuterol/budesonide fixed-dose combination rescue medication has reduced severe exacerbations.
Trial Results
The safety and tolerability of PT027 in both trials were consistent with the known profiles of the components, with the most common adverse events including headache, oral candidiasis, cough, and dysphonia. The results of the DENALI and MANDALA trials demonstrate that an albuterol/budesonide rescue inhaler can address inflammation and prevent exacerbations, making it a promising treatment option for patients with asthma.
References:
AstraZeneca. (2022, May 15). PT027, a novel fixed-dose combination of albuterol and ... - astrazeneca US. AstraZeneca. https://www.astrazeneca-us.com/media/press-releases/2022/pt027-significantly-reduced-the-risk-of-a-severe-exacerbation-compared-to-albuterol-in-patients-with-asthma.html
Hunter, E. (Ed.). (2023, January 11). FDA approves Albuterol/Budesonide Rescue Medication for asthma exacerbations. Pharmacy Times. https://www.pharmacytimes.com/view/fda-approves-albuterol-budesonide-rescue-medication-for-asthma-exacerbations
LLP, A. (2022, May 15). Avillion announces publication of positive full results from Mandala Phase III trial of AstraZeneca’s PT027 in asthma patients in the New England Journal of Medicine. PR Newswire. https://www.prnewswire.com/news-releases/avillion-announces-publication-of-positive-full-results-from-mandala-phase-iii-trial-of-astrazenecas-pt027-in-asthma-patients-in-the-new-england-journal-of-medicine-301547471.html
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