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The Food and Drug Administration’s (FDA) Pulmonary-Allergy Drugs Advisory Committee (PADAC) has voted 16 to 1 that the data support a favourable benefit risk assessment for the use of PT027 (albuterol/budesonide) for the treatment of asthma in people aged 18 years and older. In adolescents aged 12 to 17 years, the Committee voted 9 to 8 that the data do not support a favourable benefit risk assessment for the use of PT027 for the treatment of asthma. In children aged 4 to 11 years, the Committee voted 16 to 1 that the data do not support a favourable benefit risk assessment for the use of PT027 for the treatment of asthma.

PT027 is a potential first-in-class, pressurised metered-dose inhaler (pMDI), fixed-dose combination rescue medication in the US containing albuterol, a short-acting beta2-agonist (SABA), and budesonide, an anti-inflammatory inhaled corticosteroid (ICS). It is being developed by AstraZeneca and Avillion.

In the first half of 2022, the FDA accepted the New Drug Application (NDA) for PT027 and set a Prescription Drug User Fee Act date for the first half of 2023.

Bradley E. Chipps, Past President of the American College of Allergy, Asthma & Immunology and Medical Director of the Capital Allergy & Respiratory Disease Center in Sacramento, US, said: “Millions of people with asthma rely on their albuterol rescue inhaler to alleviate acute symptoms, but this does not treat the underlying inflammation, leaving patients at risk of severe asthma exacerbations, regardless of their disease severity or level of control. If approved, PT027 could transform the current rescue treatment approach.”

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “We are pleased that the Pulmonary-Allergy Drugs Advisory Committee has recognised the potential for PT027 to deliver important benefits for people with asthma, as a first-in-class treatment option in the US. We look forward to working with our partner Avillion and the FDA to progress the application and discuss next steps, including for adolescents and children.”

Asthma is a chronic, inflammatory, variable respiratory disease that affects as many as 339 million people worldwide,¹ including over 25 million in the US.² Globally, more than 176 million asthma attacks are experienced each year.³

The NDA submission was based on results from the MANDALA, DENALI and TYREE Phase III trials.^4-7 In MANDALA, PT027 significantly reduced the risk of severe exacerbations compared to albuterol in patients with moderate to severe asthma when used as an as-needed rescue medication in response to symptoms.^4,5 In DENALI, PT027 significantly improved lung function compared to the individual components, albuterol and budesonide, in patients with mild to moderate asthma.⁶

The safety and tolerability of PT027 in these trials were consistent with the known profiles of the components.^4-7

Results from the MANDALA trial were published in the in May 2022.⁴

PADAC reviews and evaluates available data concerning the safety and effectiveness of marketed and investigational human drug products for use in the treatment of pulmonary disease and diseases with allergic and/or immunologic mechanisms and makes appropriate recommendations to the Commissioner of Food and Drugs.

Notes

Asthma
Asthma is a chronic, inflammatory, variable respiratory disease that affects as many as 339 million adults and children worldwide,¹ including over 25 million in the US.²

Patients with asthma experience recurrent breathlessness and wheezing, which varies over time, and in severity and frequency.⁸ These patients are at risk of severe exacerbations regardless of their disease severity, adherence to treatment or level of control.^9,10

There are an estimated 176 million asthma exacerbations globally per year,³ including more than 10 million in the US;² these are physically threatening and emotionally significant for many patients¹¹ and can be fatal.^1,12

Inflammation is central to both asthma symptoms⁸ and exacerbations.¹³ Many patients experiencing asthma symptoms use a SABA (e.g. albuterol) as a rescue medicine;^14-16 however, taking a SABA alone does not address inflammation, leaving patients at risk of severe exacerbations,¹⁷ which can result in impaired quality of life,¹⁸ hospitalisation¹⁹ and frequent oral corticosteroid (OCS) use.¹⁹ Treatment of exacerbations with as few as 1-2 short courses of OCS are associated with an increased risk of adverse health conditions including type 2 diabetes, depression/anxiety, renal impairment, cataracts, cardiovascular disease, pneumonia and fracture.^8,20,21 International recommendations from the Global Initiative for Asthma no longer recommend SABA alone as the preferred rescue therapy.⁸

MANDALA
MANDALA^4,22 was a Phase III, randomised, double-blind, multicentre, parallel-group, event-driven trial evaluating the efficacy and safety of PT027 compared to albuterol on the risk of experiencing a severe asthma exacerbation in 3,132 adults, adolescents, and children (aged 4-11 years) with moderate to severe asthma taking ICS alone or in combination with a range of asthma maintenance therapies, including long-acting beta2-agonists (LABA), leukotriene receptor antagonists (LTRA), long-acting muscarinic antagonists (LAMA) or theophylline. The trial comprised a two-to-four-week screening period, at least a 24-week treatment period and a two-week post-treatment follow-up period.

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. PT027 and the albuterol comparator were delivered in a pressurised metered-dose inhaler (pMDI) using AstraZeneca’s Aerosphere delivery technology. The primary efficacy endpoint was the time to first severe asthma exacerbation during the treatment period. Secondary endpoints included severe exacerbation rate (annualised), total systemic corticosteroid exposure (annualised), asthma control and health-related quality of life.

Full results from the positive MANDALA Phase III trial showed that PT027 (albuterol/budesonide) demonstrated a statistically significant reduction in the risk of a severe exacerbation versus albuterol rescue in patients with moderate to severe asthma. Compared with albuterol rescue, PT027 at the 180mcg albuterol/160mcg budesonide dose reduced the risk of a severe exacerbation by 27% (p4,5

Primary and secondary endpoint results in adults and adolescents^4,5
(pre-planned on-treatment efficacy analysis)