Positive full results of MANDALA phase III trial of PT 027 in asthma patients are published in NEJM.- Avillion + AstraZeneca
Avillion LLP, a drug development company focused on the co-development and financing of pharmaceutical candidates from proof-of-concept through to regulatory approval, announces that full results from the positive MANDALA Phase III trial of AstraZeneca’s PT 027, a novel fixed-dose combination of albuterol and budesonide, have been published in the New England Journal of Medicine and were presented at the American Thoracic Society (ATS) 2022 International Conference.
The results show that PT 027 at two different strengths of budesonide, used as an as-needed rescue medicine, demonstrated a statistically significant reduction in the risk of a severe exacerbation versus albuterol rescue in patients with moderate to severe asthma.
PT 027 is a potential first-in-class inhaled, fixed-dose combination of albuterol, a short-acting beta2-agonist (SABA), and budesonide, an inhaled corticosteroid (ICS), in the US, being developed by Avillion and AstraZeneca under a 2018 clinical co-development agreement. Under the terms of the agreement, Avillion became the trial sponsor responsible for executing and funding the multicentre, global clinical trial programme for PT 027 through NDA filing to a regulatory decision in the US. Following the successful approval of PT 027, AstraZeneca has the option, upon certain financial payments, to commercialise the medicine in the US.
The full results from MANDALA demonstrate that, compared with albuterol rescue, PT 027 at the 180mcg albuterol/160mcg budesonide dose reduced the risk of a severe exacerbation by 27% (p<0.001) in adults and adolescents. in the trial, patients were randomised to receive pt 027 or albuterol rescue, on top of their usually prescribed maintenance ics, with or without additional controller medicines.in secondary endpoints, pt 027 (180mcg albuterol 160mcg budesonide) demonstrated a 33% reduction in mean annualised total systemic corticosteroid exposure (p="0.002)" and a 24% reduction in annualised severe exacerbation rate (p="0.008)." a numerically higher odds of patients experiencing an improvement in symptom control and quality of life was also observed after 24 weeks of treatment with pt027 compared to albuterol rescue.></0.001)>
Adverse events (AEs) were similar across the treatment groups in the trial and consistent with the known safety profiles of the individual components, with the most common AEs including nasopharyngitis and headache.
In the MANDALA trial, PT 027 at a lower budesonide dose (180mcg albuterol/80mcg budesonide) also demonstrated a statistically significant reduction of 17% in the risk of severe exacerbation versus albuterol rescue (p=0.041), when used as an as-needed rescue medicine in adults, adolescents and children aged 4–11 years.
Also being presented at the ATS International Conference this week are the positive DENALI Phase III trial results. In this trial, PT 027 demonstrated a statistically significant improvement in lung function measured by forced expiratory volume in one second (FEV1), compared to the individual components albuterol and budesonide, and compared to placebo in patients with mild to moderate asthma aged 12 years or older. Onset of action and duration of effect were similar for PT 027 and albuterol. The safety and tolerability of PT 027 in DENALI was consistent with the known profiles of the components.
See-Papi A, et al. "Albuterol-budesonide fixed-dose combination rescue inhaler for asthma". N Eng J Med. 2022; May 15. DOI: 10.1056/NEJMoa2203163. Online ahead of print.
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