The study marks the first time an albuterol/budesonide fixed-dose combination rescue medication has reduced severe exacerbations, the company said.
PT027 (albuterol/budesonide), at 2 different strengths of budesonide, demonstrated a statistically significant reduction in the risk of severe exacerbation versus albuterol rescue in individuals with moderate to severe asthma, AstraZeneca said in a statement.
PT027 is a potential first-in-class, fixed-dose combination rescue medication containing albuterol, a short-acting beta2-agnosit and budesonide in the United States and was developed by AstraZeneca and Avillion.
“The MANDALA phase 3 trial results demonstrated that PT027 provided additional anti-inflammatory treatment in response to patient symptoms, which led to a reduced risk of severe exacerbations compared with albuterol alone,” Bradley Chipps, MD, past president of the American College of Allergy, Asthma, & Immunology and medical director of Capital Allergy & Respiratory Disease Center in Sacramento, California, said in a statement. “These data further strengthen the growing body of evidence around the value of as-needed anti-inflammatory treatment in asthma and support PT027’s potential to transform the current rescue treatment approach.”
Compared with albuterol rescue, PT027, at the 180-mcg albuterol/160 mcg budesonide dose, reduced the risk of severe exacerbation by 27% in both adolescents and adults.
In the MANDALA phase 3 trial, investigators randomized individuals to receive either PT027 or albuterol rescue on top of their usually prescribed maintenance inhaled corticosteroid, with or without additional controller medicines.
In the secondary endpoints, PT027 demonstrated a 33% reduction in mean annualized total systemic corticosteroid exposure and a 24% reduction in annualized severe exacerbation rate.
A numerically higher odds of individuals experiencing an improvement in quality of life and symptom control was observed after 34 weeks of treatment with PT027 compared with the albuterol rescue.
“The results from these phase 3 trials support the clinical benefit of PT027, an albuterol/budesonide rescue inhaler, which has the potential to be a first-in-class treatment approach that can prevent asthma attacks over and above their current maintenance therapies,” Mene Pangalos, PhD, executive vice president of BioPharmaceuticals R&D at AstraZeneca, said in the statement.
Adverse events (AEs) were similar across the treatment groups in the trial and were consistent with the known safety profile of the individual components. The most common AEs were headaches and nasopharyngitis.
Additionally, PT027 at a lower budesonide dose, at 180 mcg of albuterol and 80 mcg budesonide, also demonstrated a statistically significant reduction of 17% in the risk of severe exacerbation versus albuterol rescue when used as needed rescue medicine in individuals aged 11 years and older.
The results were published in the New England Journal of Medicine and will be presented at the American Thoracic Society 2022 International Conference.
Furthermore, positive results of the DENALI phase 3 trial will be presented at the conference.
In this trial, PT027 demonstrated a statistically significant improvement in lung function measured by forced expiratory volume in 1 second compared with the individual components, albuterol and budesonide, and compared with the placebo, in individuals with mild to moderate asthma aged 12 years or older.
The onset of action and duration of effect were similar for albuterol and PT027. Additionally, the safety and tolerability of PT027 in DENALI was consistent with known profiles of the components.
PT027, a novel fixed-dose combination of albuterol and budesonide, used as an as-needed rescue medicine, significantly reduced the risk of a severe exacerbation compared to albuterol by 27% in patients with asthma. AstraZeneca. News release. May 15, 2022. Accessed May 16, 2022. https://www.astrazeneca.com/media-centre/press-releases/2022/pt027-significantly-reduced-the-risk-of-a-severe-exacerbation-compared-to-albuterol-in-patients-with-asthma.html