PT027 Phase III trials met primary endpoints

PT027 Phase III trials met primary endpoints 

9 September 2021 07:00 BST 
AstraZeneca 

Fixed-dose combination of albuterol and budesonide (PT027) demonstrated significant benefits for asthma patients in MANDALA and DENALI Phase III trials  

PT027 significantly reduced the risk of severe exacerbations compared to albuterol in patients with moderate to severe asthma in MANDALA trial when used as a rescue medicine in response to symptoms 

PT027 significantly improved lung function compared to individual components in mild to moderate asthma in DENALI trial 

Positive high-level results from the MANDALA and DENALI Phase III trials of PT027 (albuterol/budesonide), at both 180/160mcg and 180/80mcg doses, met all primary endpoints demonstrating statistically significant benefits in patients with asthma versus individual components albuterol, also known as salbutamol (180mcg) and budesonide (160mcg).  

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), being developed by AstraZeneca and Avillion. 

The MANDALA trial met the primary endpoint, with PT027 demonstrating statistically significant and clinically meaningful reductions in the risk of severe exacerbations compared to albuterol, when used as a rescue medicine in response to symptoms. The trial included 3,132 patients with moderate to severe asthma taking maintenance ICS with or without additional controller medicines. 

The DENALI trial met the dual primary endpoints, with PT027 showing 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. The trial included 1,001 patients with mild to moderate asthma previously treated either with a SABA as needed alone or in addition to low-dose maintenance ICS therapy. 

Asthma is a chronic, inflammatory, fluctuating respiratory disease¹ that affects as many as 339 million adults and children worldwide,¹ including over 25 million in the US.² Inflammation is a distinctive feature of asthma³ and plays a key role in asthma symptoms,⁴ exacerbations⁵ and deaths.⁵ 

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: “Severe asthma exacerbations are a significant burden for many asthma patients of all ages resulting in impaired quality of life, hospitalisation, treatment with systemic corticosteroids which can lead to serious side effects, and the possibility of premature death. Many millions of patients globally rely on their rescue inhaler to alleviate acute symptoms, but this does not treat the underlying inflammation in asthma. The MANDALA and DENALI trials demonstrate an albuterol/budesonide rescue inhaler can address inflammation and prevent exacerbations, making PT027 an important potential new treatment option for patients.” 

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “All patients with asthma are at risk of severe exacerbations, regardless of their disease severity and many are known to overuse short-acting bronchodilators. These exciting results with PT027 bring us one step closer to providing an innovative and superior treatment approach for asthma by preventing exacerbations.” 

The safety and tolerability of PT027 in both trials were consistent with the known profiles of the components. Detailed data from MANDALA and DENALI will be presented at an upcoming medical meeting.