First and only rescue medication approved in
the US for as-needed use to reduce risk of asthma
exacerbations
AIRSUPRA™ (albuterol/budesonide), formerly known as PT027, has
been approved in the US for the as-needed treatment or prevention
of bronchoconstriction and to reduce the risk of exacerbations in
people with asthma aged 18 years and older.
The approval by the Food and Drug Administration (FDA) was based
on results from the MANDALA and DENALI Phase III trials.1,2 In
MANDALA, AIRSUPRA 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.1 Importantly, in the secondary endpoint of
mean annualized total systemic corticosteroid exposure, AIRSUPRA
demonstrated a significant reduction compared to albuterol at the
approved dose of 180mcg albuterol/160mcg budesonide.1 In DENALI,
AIRSUPRA significantly improved lung function compared to the
individual components albuterol and budesonide in patients with
mild to moderate asthma.2
AIRSUPRA is a first-in-class, pressurized metered-dose inhaler
(pMDI), fixed-dose combination rescue medication containing
albuterol, a short-acting beta2-agonist (SABA), and budesonide, an
anti-inflammatory inhaled corticosteroid (ICS) in the US. It is
being developed by AstraZeneca and Avillion.
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:
“People with asthma are at risk of severe exacerbations regardless
of their disease severity or level of control. Current albuterol
rescue inhalers alleviate acute symptoms, but do not treat the
underlying inflammation in asthma. The approval of AIRSUPRA means
that for the first time, adults with asthma in the US have a rescue
treatment to manage both their symptoms and the inflammatory nature
of their disease.”
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, AstraZeneca, said: “With patients experiencing more than
10 million asthma exacerbations each year in the US and
uncontrolled asthma expected to cost the US economy billions of
dollars in direct medical costs alone over the next 20 years,
today’s positive decision is good news for those adults with asthma
who make up more than 80% of asthma patients in the US. Physicians
will be able to offer their patients AIRSUPRA, an important new
rescue treatment that reduces the risk of asthma
exacerbations.”
Asthma is a chronic, inflammatory respiratory disease with
variable symptoms that affects as many as 262 million people
worldwide.3 In the US over 21 million adults have asthma,
representing more than 80% of the total number of people with
asthma.4 Adults have 8.5 million exacerbations each year in the
US.4 Uncontrolled asthma will cost the US economy an estimated $300
billion (in 2018 dollar values) in the next 20 years in direct
medical costs alone.5
The safety and tolerability of AIRSUPRA in both trials were
consistent with the known profiles of the components,1,2 with the
most common adverse events including headache, oral candidiasis,
cough and dysphonia.6
Results from the MANDALA trial were published in the
New England Journal of Medicine in May
2022.1
INDICATION
AIRSUPRA is a combination of albuterol, a beta2-adrenergic
agonist and budesonide, a corticosteroid, indicated for the
as-needed treatment or prevention of bronchoconstriction and to
reduce the risk of exacerbations in patients with asthma 18 years
of age and older.
IMPORTANT SAFETY INFORMATION
- Contraindications: Hypersensitivity to albuterol,
budesonide, or to any of the excipients
- Deterioration of Asthma: Asthma may deteriorate acutely
over a period of hours or chronically over several days or longer.
If the patient continues to experience symptoms after using
AIRSUPRA or requires more doses of AIRSUPRA than usual, it may be a
marker of destabilization of asthma and requires evaluation of the
patient and their treatment regimen
- Paradoxical Bronchospasm: AIRSUPRA can produce
paradoxical bronchospasm, which may be life threatening.
Discontinue AIRSUPRA immediately and institute alternative therapy
if paradoxical bronchospasm occurs. It should be recognized that
paradoxical bronchospasm, when associated with inhaled
formulations, frequently occurs with the first use of a new
canister
- Cardiovascular Effects: AIRSUPRA, like other drugs
containing beta2-adrenergic agonists, can produce clinically
significant cardiovascular effects in some patients, as measured by
pulse rate, blood pressure, and/or other symptoms. If such effects
occur, AIRSUPRA may need to be discontinued. In addition,
beta-agonists have been reported to produce electrocardiogram (ECG)
changes, such as flattening of the T wave, prolongation of the QTc
interval, and ST-segment depression. Therefore, AIRSUPRA, like all
sympathomimetic amines, should be used with caution in patients
with cardiovascular disorders, especially coronary insufficiency,
cardiac arrhythmias, and hypertension
- Do Not Exceed Recommended Dose: Clinically significant
cardiovascular effects and fatalities have been reported in
association with excessive use of inhaled sympathomimetic
drugs
- Hypersensitivity Reactions, Including Anaphylaxis: Can
occur after administration of albuterol sulfate and budesonide,
components of AIRSUPRA, as demonstrated by cases of anaphylaxis,
angioedema, bronchospasm, oropharyngeal edema, rash, and urticaria.
Discontinue AIRSUPRA if such reactions occur
- Risk of Sympathomimetic Amines with Certain Coexisting
Conditions: AIRSUPRA, like all therapies containing
sympathomimetic amines, should be used with caution in patients
with convulsive disorders, hyperthyroidism, or diabetes mellitus
and in patients who are unusually responsive to sympathomimetic
amines
- Hypokalemia: Beta-adrenergic agonist medicines may
produce significant hypokalemia in some patients. The decrease in
serum potassium is usually transient, not requiring
supplementation
- Immunosuppression and Risk of Infections: Due to
possible immunosuppression from use of ICS, potential worsening of
infections could occur. Use with caution. A more serious or fatal
course of chickenpox or measles can occur in susceptible
patients
- Oropharyngeal Candidiasis: Has occurred in patients
treated with ICS agents. Monitor patients periodically. Advise
patients to rinse his/her mouth with water, if available, without
swallowing after inhalation
- Hypercorticism and Adrenal Suppression: May occur with
very high doses in susceptible individuals. If such changes occur,
consider appropriate therapy
- Reduction in Bone Mineral Density: Decreases in bone
mineral density have been observed with long-term administration of
ICS. For patients at high risk for decreased bone mineral density,
assess initially and periodically thereafter
- Glaucoma and Cataracts: Have been reported following the
long-term administration of ICS, including budesonide, a component
of AIRSUPRA
- Effects on Growth: Orally inhaled corticosteroids,
including budesonide, may cause a reduction in growth velocity when
administered to pediatric patients. The safety and effectiveness of
AIRSUPRA have not been established in pediatric patients, and
AIRSUPRA is not indicated for use in this population
- Most common adverse reactions (incidence ≥ 1%) are
headache, oral candidiasis, cough, and dysphonia
- Drug Interactions: AIRSUPRA should be administered with
caution to patients being treated with:
- Strong cytochrome P450 3A4 inhibitors (may cause systemic
corticosteroid effects)
- Short-acting bronchodilators (concomitant use of additional
beta-agonists with AIRSUPRA should be used judiciously to prevent
beta-agonist overdose)
- Beta-blockers (may block pulmonary effects of beta-agonists and
produce severe bronchospasm)
- Diuretics or non-potassium-sparing diuretics (may potentiate
hypokalemia or ECG changes). Consider monitoring potassium
levels
- Digoxin (may decrease serum digoxin levels). Consider
monitoring digoxin levels
- Monoamine oxidase inhibitors (MAOI) and tricyclic
antidepressants (Use AIRSUPRA with extreme caution; may potentiate
effect of albuterol on the cardiovascular system)
- Use AIRSUPRA with caution in patients with hepatic impairment,
as budesonide systemic exposure may increase. Monitor patients with
hepatic disease
Please see full Prescribing Information, including Patient
Information.
Notes
Asthma
Asthma is a chronic, inflammatory respiratory disease with
variable symptoms that affects as many as 262 million people
worldwide,3 including over 25 million in the US.4
Patients with asthma experience recurrent breathlessness and
wheezing, which varies over time, and in severity and frequency.7
These patients are at risk of severe exacerbations regardless of
their disease severity, adherence to treatment or level of
control.8,9
There are an estimated 136 million asthma exacerbations globally
per year,10 including more than 10 million in the US;4 these are
physically threatening and emotionally significant for many
patients11 and can be fatal.3,12
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 hospitalization19 and frequent oral corticosteroid (OCS)
use.19 Treatment of exacerbations with as few as 1-3 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.20 International recommendations from the Global
Initiative for Asthma no longer recommend SABA alone as the
preferred rescue therapy.7
MANDALA, DENALI and the CREST (Combination REliever
STudies) program
The CREST clinical trial program studied the efficacy and safety
of PT027 and included the MANDALA,1,21,22 DENALI2,23,24 and TYREE25
Phase III trials.
MANDALA1,21,22 was a Phase III, randomized, double-blind,
multicenter, parallel-group, event-driven trial evaluating the
efficacy and safety of AIRSUPRA compared to albuterol on the time
to first 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: AIRSUPRA 180/160mcg (excluding
children aged 4–11 years), albuterol/budesonide 180/80mcg or
albuterol 180mcg, taken as an as-needed rescue medicine. AIRSUPRA
and the albuterol comparator were delivered in a 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 (annualized), total systemic corticosteroid
exposure (annualized), asthma control and health-related quality of
life.
Results from the positive MANDALA Phase III trial showed that
AIRSUPRA demonstrated a statistically significant reduction in the
risk of a severe exacerbation versus albuterol rescue in patients
with moderate to severe asthma.1,22 Compared with albuterol rescue,
AIRSUPRA at the 180mcg albuterol/160mcg budesonide dose reduced the
risk of a severe exacerbation by 27% (p<0.001) in adults and
adolescents.1,22
Primary and secondary endpoint results in adults and
adolescents1,22 (pre-planned on-treatment efficacy
analysis)
Treatment Group
Comparison versus albuterol
180mcg
Time to first severe
exacerbation
n
Number (%) of Patients with a
Severe Exacerbation a, b
Hazard Ratio (95% CI)
p value (2‑sided)
AIRSUPRA 180/160mcg
1013
207 (20.4)
0.73 (0.61, 0.88)
<0.001
Albuterol 180mcg
1014
266 (26.2)
Annualized severe exacerbation
rate (rate ratio)
n
Number of Severe Exacerbations
a, b
Annualized rate (95%
CI)
Rate Ratio (95% CI)
AIRSUPRA 180/160mcg
1013
334
0.45 (0.34, 0.60)
0.76 (0.62, 0.93)
Albuterol 180mcg
1014
413
0.59 (0.44, 0.78)
Annualized total SCS dose
(mg/year)
n
Mean (SD) b
% reduction in mean
AIRSUPRA 180/160mcg
1012
86.2 (262.86)
33.4%
Albuterol 180mcg
1011
129.3 (657.19)
aDeterioration of asthma requiring use of
SCS for ≥3 days, or inpatient hospitalization, or emergency room
visit, that required SCS. bBefore discontinuation of randomized
treatment or change in maintenance therapy. CI, confidence
interval; SCS, systemic corticosteroid; SD, standard deviation
Primary endpoint results in adults, adolescents, and
children1,22 (pre-planned on-treatment efficacy analysis)
Treatment Group
Comparison versus albuterol
180mcg
Time to first severe
exacerbation
n
Number (%) of Patients with a
Severe Exacerbation a, b
Hazard Ratio (95% CI)
p value (2‑sided)
Albuterol/budesonide
180/80mcg
1054
241 (22.9)
0.83 (0.70, 0.99)
0.041
Albuterol 180mcg
1056
276 (26.1)
aDeterioration of asthma requiring use of
SCS for ≥3 days, or inpatient hospitalization, or emergency room
visit, that required SCS. bBefore discontinuation of randomized
treatment or change in maintenance therapy. CI, confidence
interval
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.1,22
DENALI2,23,24 was a Phase III, randomized, double-blind,
placebo-controlled, multicenter, parallel-group trial evaluating
the efficacy and safety of AIRSUPRA compared to its components
albuterol and budesonide on improvement in lung function in 1,001
adults, adolescents, and children aged 4–11 years with mild to
moderate asthma previously treated either with SABA as-needed alone
or in addition to regular low-dose ICS maintenance therapy. The
trial comprised a two-to-four-week screening period, a 12-week
treatment period and a two-week post-treatment follow-up
period.
Patients were randomly assigned to one of the following five
treatment groups in a 1:1:1:1:1 ratio: AIRSUPRA 180/160mcg four
times daily (excluding children aged 4–11 years),
albuterol/budesonide 180/80mcg four times daily, albuterol 180mcg
four times daily, budesonide 160mcg four times daily (excluding
children aged 4–11 years) and placebo four times daily. AIRSUPRA,
the albuterol and budesonide comparators and placebo were delivered
in a pMDI using AstraZeneca’s Aerosphere delivery technology. The
dual primary efficacy endpoints were change from baseline in FEV1
area under the curve 0-6 hours over 12 weeks of AIRSUPRA compared
to budesonide to assess the effect of albuterol and change from
baseline in trough FEV1 at Week 12 of AIRSUPRA compared to
albuterol to assess the effect of budesonide. Secondary endpoints
included the time to onset and duration of response on day one,
number of patients who achieved a clinically meaningful improvement
in asthma control from baseline at Week 12 and trough FEV1 at Week
1.
In the trial, AIRSUPRA 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 AIRSUPRA and albuterol. The
safety and tolerability of AIRSUPRA in DENALI was consistent with
the known profiles of the components.
AIRSUPRA
AIRSUPRA (albuterol/budesonide), formerly known as PT027, is a
first-in-class SABA/ICS rescue treatment for asthma in the US, to
be taken as needed. It is an inhaled, fixed-dose combination rescue
medication containing albuterol (also known as salbutamol), a SABA,
and budesonide, a corticosteroid, and has been developed in a pMDI
using AstraZeneca’s Aerosphere delivery technology.
AstraZeneca and Avillion collaboration
In March 2018, AstraZeneca and Avillion signed an agreement to
advance AIRSUPRA through a global clinical development program for
the treatment of asthma. Under the terms of the agreement, Avillion
became the trial sponsor responsible for executing and funding the
multicenter, global clinical trial program for AIRSUPRA through NDA
filing to a regulatory decision in the US. Following the successful
approval of AIRSUPRA, AstraZeneca has the option, upon certain
financial payments, to commercialize the medicine in the US.
AstraZeneca in Respiratory and Immunology
Respiratory & Immunology, part of BioPharmaceuticals, is one
of AstraZeneca’s main disease areas and is a key growth driver for
the Company.
AstraZeneca is an established leader in respiratory care with a
50-year heritage. The Company aims to transform the treatment of
asthma and COPD by focusing on earlier biology-led treatment,
eliminating preventable asthma attacks, and removing COPD as a
top-three leading cause of death. The Company’s early respiratory
research is focused on emerging science involving immune
mechanisms, lung damage and abnormal cell-repair processes in
disease and neuronal dysfunction.
With common pathways and underlying disease drivers across
respiratory and immunology, AstraZeneca is following the science
from chronic lung diseases to immunology-driven disease areas. The
Company’s growing presence in immunology is focused on five mid- to
late-stage franchises with multi-disease potential, in areas
including rheumatology (including systemic lupus erythematosus),
dermatology, gastroenterology, and systemic eosinophilic-driven
diseases. AstraZeneca’s ambition in Respiratory & Immunology is
to achieve disease modification and durable remission for millions
of patients worldwide.
AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company
that focuses on the discovery, development and commercialization of
prescription medicines in Oncology, Rare Diseases and
BioPharmaceuticals, including Cardiovascular, Renal &
Metabolism, and Respiratory & Immunology. Based in Cambridge,
UK, AstraZeneca operates in over 100 countries, and its innovative
medicines are used by millions of patients worldwide. For more
information, please visit www.astrazeneca-us.com and follow us on
Twitter @AstraZenecaUS.
References
- Papi A, et al. Albuterol–Budesonide Fixed-Dose Combination
Rescue Inhaler for Asthma. N Engl J Med 2022; 386 (22):
2071-2083.
- Chipps BE, et al. Efficacy and safety of albuterol/budesonide
(PT027) in mild-to-moderate asthma: Results of the DENALI study. Am
J Respir Crit Care Med 2022; 205: A3414. Abstract. Available at:
https://doi.org/10.1164/ajrccm-conference.2022.205.1_MeetingAbstracts.A3414
[Last accessed: November 2022].
- The Global Asthma Network. The Global Asthma Report 2022.
[Online]. Available at: http://globalasthmareport.org/index.html
[Last accessed: November 2022].
- CDC. Most Recent National Asthma Data. [Online]/ Available at:
https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm.
[Last accessed: November 2022].
- Yaghoubi M, et al. The Projected Economic and Health Burden of
Uncontrolled Asthma in the United States. Am J Respir Crit Care
Med. 2019; 200 (9): 1102-1112.
- Airsupra (albuterol/budesonide) US prescribing information;
2023.
- Global Initiative for Asthma. Global strategy for asthma
management and prevention, 2022. Available at:
https://ginasthma.org/wp-content/uploads/2022/07/GINA-Main-Report-2022-FINAL-22-07-01-WMS.pdf.
[Last accessed: November 2022].
- Price D, et al. Asthma control and management in 8,000 European
patients: the REcognise Asthma and LInk to Symptoms and Experience
(REALISE) survey. NPJ Prim Care Respir Med. 2014; 24: 14009.
- Papi A, et al. Relationship of inhaled corticosteroid adherence
to asthma exacerbations in patients with moderate-to-severe asthma.
J Allergy Clin Immunol Pract. 2018; 6 (6): 1989-98.e3.
- AstraZeneca Pharmaceuticals. Data on File.
Budesonide/formoterol Data on File: Annual Rate of Asthma
Exacerbations Globally. (REF-173201)
- Sastre J, et al. Insights, attitudes, and perceptions about
asthma and its treatment: a multinational survey of patients from
Europe and Canada. World Allergy Organ J. 2016; 9: 13.
- Fernandes AG, et al. Risk factors for death in patients with
severe asthma. J Bras Pneumol. 2014; 40 (4): 364-372.
- Wark PA, et al. Asthma exacerbations· 3: pathogenesis. Thorax.
2006; 61 (10): 909-15.
- Johnson DB, et al. Albuterol. 2022 May 1. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–.
PMID: 29489143.
- Montemayor T, et al. Albuterol: Often Used and Heavily Abused.
Respiratory Care November 2021, 66 (Suppl 10) 3603775.
- ClinCalc.com. Albuterol: Drug Usage Statistics, US 2013 – 2020.
Available at: https://clincalc.com/DrugStats/Drugs/Albuterol. [Last
accessed: November 2022].
- Nwaru BI, et al. Overuse of short-acting β2-agonists in asthma
is associated with increased risk of exacerbation and mortality: a
nationwide cohort study of the global SABINA programme. Eur Respir
J. 2020; 55 (4): 1901872.
- Lloyd A, et al. The impact of asthma exacerbations on
health-related quality of life in moderate to severe asthma
patients in the UK. Prim Care Respir J. 2007; 16 (1): 22-7.
- Bourdin A, et al. ERS/EAACI statement on severe exacerbations
in asthma in adults: facts, priorities and key research questions.
Eur Respir J. 2019; 54 (3): 1900900.
- Price DB, et al. Adverse outcomes from initiation of systemic
corticosteroids for asthma: long-term observational study. J Asthma
Allergy. 2018; 11: 193–204.
- Chipps BE, et al. Evaluation of the Efficacy and Safety of
As-Needed PT027 Budesonide/Albuterol MDI) Compared to As-Needed
Albuterol MDI in Adults and Children 4 Years of Age or Older with
Uncontrolled Moderate to Severe Asthma: Design of the MANDALA
Study. Am J Respir Crit Care Med. 2020; 201: A3015.
- Papi A, et al. Efficacy and safety of as-needed
albuterol/budesonide versus as-needed albuterol in adults,
adolescents and children aged ≥4 years with moderate-to-severe
asthma: Results of the MANDALA study. American Thoracic Society
International Conference 2022. Oral Presentation. Abstract A3413
during B93. BREAKTHROUGHS IN PEDIATRIC AND ADULT ASTHMA CLINICAL
TRIALS.
- Clinicaltrials.gov. A Study to Assess the Efficacy and Safety
of Budesonide/Albuterol Metered-dose Inhaler (BDA MDI/PT027) Used 4
Times Daily in Adults and Children 4 Years of Age or Older With
Asthma (DENALI). Available at
https://clinicaltrials.gov/ct2/show/NCT03847896. [Last accessed:
November 2022].
- AstraZeneca Pharmaceuticals. Data on File. DENALI clinical
trial protocol Data on File (ID: 121792).
- LaForce C, et al. Albuterol/budesonide for the treatment of
exercise-induced bronchoconstriction in patients with asthma: The
TYREE study. Ann Allergy Asthma Immunol. 2022; 128: 169-177.
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