AstraZeneca's PT027 (Albuterol/Budesonide) Phase 3 Trial Shows 27% Reduction in Severe Asthma Exacerbations as an As-Needed Rescue Therapy

News on May 16, 2022 /BioValleyBIOON/ -- AstraZeneca recently announced complete results from the positive MANDALA Phase 3 clinical trial: In patients with moderate to severe asthma, PT027 (albuterol/budesonide, 180/160mcg or 180/80mcg) at two different budesonide dose strengths, when used as an as-needed rescue medication, compared with albuterol rescue,StatisticsSignificantly reduced the risk of severe asthma exacerbations in studies. Notably,This is the first confirmation that a fixed-dose combination rescue medication of salbutamol/budesonide can reduce severe asthma exacerbations.

PT027, developed in collaboration by AstraZeneca and Avillion, is a potential first-in-class, inhaled, fixed-dose combination product consisting of albuterol (a short-acting beta-2 agonist [SABA]) and budesonide (an inhaled corticosteroid [ICS]). Globally, there are more than 176 million asthma attacks each year.

In the MANDALA trial, patients with moderate to severe asthma receiving maintenance therapy with ICS (with or without other medications) were randomly assigned to receive PT027 or salbutamol for rescue. The data showed that, in adult and adolescent patients,Compared with salbutamol rescue, PT027 at a higher budesonide dose intensity (salbutamol/budesonide, 180/160mcg) significantly reduced the risk of severe exacerbation by 27% (p<0.001).。

For secondary endpoints, PT027 (albuterol/budesonide, 180/160mcg) demonstrated a 33% reduction in the mean annualized total systemic corticosteroid (SCS) exposure (p=0.002) and a 24% reduction in annualized severe exacerbations (p=0.008). Additionally, compared with albuterol rescue therapy, treatment with PT027 (albuterol/budesonide, 180/160mcg) for 24 weeks resulted in improved patient symptom control andQuality of LifeThe probability of improvement is also higher numerically.

MANDALA trial data also showed: in adults, adolescents and 4-11 years oldChildrenIn patients using it as a rescue medication on demand, PT027 at a lower budesonide dose strength (albuterol/budesonide, 180/80mcg) significantly reduced the risk of severe exacerbations by 17% (p=0.041) compared to albuterol rescue. In the trial, adverse events (AEs) were similar across treatment groups and consistent with the known safety profiles of the individual components, with the most common AEs being nasopharyngitis and headache.

The results of the aforementioned MANDALA trial have been published in The New England Journal of Medicine (NEJM) and were presented at the 2022 American Thoracic Society (ATS) International Conference held last week.

Positive results from the DENALI Phase 3 trial were also presented at the ATS International Conference. The trial enrolled 1,001 patients with mild to moderate asthma who were previously treated with on-demand SABA alone or in combination with low-dose maintenance ICS. The data showed that, in patients aged 12 years or older with mild to moderate asthma, as measured by forced expiratory volume in one second (FEV1), compared with the individual components salbutamol and budesonide, as well as with placebo,PT027 Treatment Results in Statistically Significant Improvement in Patients' Lung FunctionThe onset time and duration of action of PT027 and salbutamol are similar. In the DENALI trial, the safety and tolerability of PT027 were consistent with the known characteristics of its components.

Chemical Structure of Salbutamol (Source: glpbio.com)

Asthma is a chronic, inflammatory, fluctuating respiratory disease that affects up to 339 million adults and children worldwide, including more than 25 million people in the United States. Inflammation is a hallmark of asthma and plays a key role in asthma symptoms, exacerbations, and mortality.

American Academy of Allergy, Asthma andImmunityBradley E. Chipps, former president of the College and Medical Director of the Sacramento Allergy and Respiratory Disease Center in the United States, stated: "The results of the MANDALA Phase 3 trial show that PT027, when used as needed, provides additional anti-inflammatory treatment to address patients' symptoms and significantly reduces the risk of severe exacerbations compared to salbutamol. These data further strengthen the growing body of evidence demonstrating the value of on-demand anti-inflammatory treatment for asthma patients and support the potential of PT027 to change the current rescue treatment approach."

Mene Pangalos, Executive Vice President of AstraZeneca's Biopharmaceuticals R&D, stated: "Asthma is an inflammatory and variable disease. Regardless of the severity of the condition or treatment adherence, patients are at risk of experiencing severe exacerbations. The results of these Phase III trials support the clinical benefits of PT027, a rescue inhaler combining albuterol and budesonide, which has the potential to become a first-of-its-kind treatment that can be used in addition to a patient’s existing maintenance therapy."Prevention"Asthma attack."

Chemical Structure of Budesonide (Source: chemsrc.com)

Patients with asthma experience recurrent episodes of breathlessness and wheezing, the severity and frequency of which vary over time. Regardless of disease severity, treatment adherence, or level of control, these patients are at risk of severe exacerbations.

It is estimated that 176 million asthma exacerbations occur globally each year, including over 10 million in the United States; for many patients, these episodes pose significant physical threats and emotional impacts, and can potentially be fatal.

Inflammation is at the core of asthma symptoms and exacerbations. Many patients experiencing asthma symptoms use SABA as a rescue medication, but the use of SABA alone does not address inflammation, leaving patients at risk of severe exacerbations, which can lead to a decline in quality of life, hospitalizations, and frequent use of oral corticosteroids (OCS). However, even just 1-2 short courses of OCS treatment during asthma exacerbations increase the risk of adverse health outcomes, including type 2Diabetes, Depression/Anxiety, Renal Impairment, Cataracts, HeartBlood VesselDiseases, pneumonia, fractures. International recommendations from the Global Initiative for Asthma no longer recommend SABA as the first-line rescue therapy. (Bioon.com)

Source of the original text: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