Avillion Reports Publication of Positive Results from AstraZeneca's (AZN) MANDALA Phase III of PT027

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 (NASDAQ: AZN) PT027, a novel fixed-dose combination of albuterol and budesonide, have been published in the New England Journal of Medicine and will be presented at the American Thoracic Society (ATS) 2022 International Conference.1.2,3 The results show that PT027 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.1,2

PT027 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 PT027 through NDA filing to a regulatory decision in the US. Following the successful approval of PT027, AstraZeneca has the option, upon certain financial payments, to commercialise the medicine in the US.

Globally, more than 176 million asthma attacks are experienced each year.10

The full results from MANDALA demonstrate that, compared with albuterol rescue, PT027 at the 180mcg albuterol/160mcg budesonide dose reduced the risk of a severe exacerbation by 27% (p<0.001) in adults and adolescents.1,2 In the trial, patients were randomised to receive PT027 or albuterol rescue, on top of their usually prescribed maintenance ICS, with or without additional controller medicines.1,2

In secondary endpoints, PT027 (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).1,2 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.1,2

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.1

Allison Jeynes, MD, Chief Executive Officer of Avillion, said: "Building on the positive high-level results for MANDALA and DENALI announced in September last year, it's fantastic to receive further confirmation of PT027's potential in reducing the significant burden that asthma presents to millions of people worldwide. With the completion of this pivotal programme, Avillion maintains its 100% trial success rate across multiple therapy areas. This is an impressive achievement and demonstrates the power of our clinical co-development model and the quality of our international team in advancing vital drugs in partnership with pharma and biotech companies. We have enjoyed an excellent collaboration with AstraZeneca, under which we have delivered these large and complex trials during a pandemic and have ongoing regulatory responsibility for the NDA filing. Furthermore, this partnership has recently expanded to include a new decentralized, randomised trial in patients with mild asthma, which is anticipated to kick off in the coming months."

Bradley E. Chipps, Past President of the American College of Allergy, Asthma & Immunology and Medical Director of Capital Allergy & Respiratory Disease Center in Sacramento, US, said: "The MANDALA Phase III trial results demonstrated that PT027, a novel fixed-dose combination of albuterol/budesonide, used as-needed, provided additional anti-inflammatory treatment in response to patient symptoms, which led to a reduced risk of severe exacerbations compared with albuterol alone. 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."

In the MANDALA trial, PT027 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.1,2

Also being presented at the ATS International Conference this week are the positive DENALI Phase III trial results. In this trial, PT027 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 PT027 and albuterol. The safety and tolerability of PT027 in DENALI was consistent with the known profiles of the components.4

The PT027 clinical co-development programme was funded by Blackstone Life Sciences, Royalty Pharma (Nasdaq: RPRX) and Abingworth.

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