REG - AstraZeneca PLC - Airsupra (PT027) approved in US for asthma

AstraZenecaAnnouncement

11/01/2023 13:00

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RNS Number : 4249M  AstraZeneca PLC  11 January 2023

11 January 2023 13:00 GMT

 

Airsupra (PT027) approved in the US for asthma

 

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 annualised 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, pressurised 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 (https://www.nejm.org/doi/10.1056/NEJMoa2203163) in May 2022.(1)

 

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 patients(11) and can be fatal.(3,12)

 

Inflammation is central to both asthma symptoms(8) 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) hospitalisation(19) 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) programme

The CREST clinical trial programme studied the efficacy and safety of PT027
and included the MANDALA,(1,21,22) DENALI(2,23,24) and TYREE(25) Phase III
trials.

 

MANDALA(1,21,22) was a Phase III, randomised, double-blind, multicentre,
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 (annualised),
total systemic corticosteroid exposure (annualised), 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 adolescents(1,22)
(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        p value (2‑sided)

(95% CI)
 Airsupra 180/160mcg                               1013    207 (20.4)                                                0.73 (0.61, 0.88)   <0.001
 Albuterol 180mcg                                  1014    266 (26.2)
 Annualised severe exacerbation rate (rate ratio)  n       Number of Severe Exacerbations (a, b)                     Annualised rate     Rate Ratio

(95% CI)
(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)
 Annualised 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)

(a)Deterioration of asthma requiring use of SCS for ≥3 days, or inpatient
hospitalisation, or emergency room visit, that required SCS. (b)Before
discontinuation of randomised treatment or change in maintenance therapy.

CI, confidence interval; SCS, systemic corticosteroid; SD, standard deviation

 

Primary endpoint results in adults, adolescents, and children(1,22)

(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        p value (2‑sided)

(95% CI)
 Albuterol/budesonide  180/80mcg    1054    241 (22.9)                                                0.83 (0.70, 0.99)   0.041
 Albuterol 180mcg                   1056    276 (26.1)

(a)Deterioration of asthma requiring use of SCS for ≥3 days, or inpatient
hospitalisation, or emergency room visit, that required SCS. (b)Before
discontinuation of randomised 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)

 

DENALI(2,23,24) was a Phase III, randomised, double-blind, placebo-controlled,
multicentre, 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 programme for the treatment of
asthma. Under the terms of the agreement, Avillion became the trial sponsor
responsible for executing and funding the multicentre, global clinical trial
programme 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 commercialise 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 (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical
company that focuses on the discovery, development, and commercialisation 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.
Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

 

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Adrian Kemp

Company Secretary

AstraZeneca PLC

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