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FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
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the
Securities Exchange Act of 1934
For the
month of August
2019
Commission
File Number: 001-11960
AstraZeneca PLC
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Breztri
Aerosphere Phase III ETHOS trial met its primary endpoint in
chronic obstructive pulmonary disease
This announcement contains inside information
28 August 2019 07:00 BST
Breztri
Aerosphere Phase III ETHOS
trial met its primary endpoint in chronic obstructive pulmonary
disease
At both standard and low budesonide doses, the triple-combination
therapy showed a statistically-significant reduction in the rate of
moderate or severe exacerbations compared with dual-combination
therapies
First time the benefit of two doses of a fixed triple-combination
therapy has been established in a Phase III chronic obstructive
pulmonary disease trial
AstraZeneca today announced positive results from the Phase III
ETHOS trial for triple-combination therapy Breztri
Aerosphere, formerly PT010, in
patients with moderate to very severe chronic obstructive pulmonary
disease (COPD).
At the standard budesonide dose, Breztri
Aerosphere (budesonide/glycopyrronium/formoterol
fumarate 320/14.4/9.6mcg) demonstrated a
statistically-significant reduction in the rate of
moderate or severe exacerbations compared with
dual-combination therapies Bevespi
Aerosphere(glycopyrronium/formoterol fumarate 14.4/9.6mcg)
and PT009 (budesonide/formoterol fumarate
320/9.6mcg).
At half of the budesonide dose, Breztri
Aerosphere (budesonide/glycopyrronium/formoterol
fumarate 160/14.4/9.6mcg) also demonstrated a
statistically-significant reduction in the rate of moderate or
severe exacerbations compared with Bevespi
Aerosphere and
PT009.
The dual-combination therapies used as comparators in the trial
represent recommended therapeutic classes for the treatment of
COPD.1
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, said: "Exacerbations are devastating events for patients
and can lead to a permanent loss of lung function. The Phase
III ETHOS trial builds on the Phase III KRONOS data which together
show Breztri
Aerosphere'sability to reduce
exacerbation risk in a broad range of patients with COPD,
irrespective of whether they have had an exacerbation in the
previous twelve months. We look forward to sharing these results
with health authorities as soon as possible."
Klaus Rabe, Professor of Pulmonary Medicine at the University of
Kiel, Director of the Department of Pneumology at Clinic
Grosshansdorf, Germany, and Lead Investigator of the ETHOS trial,
said: "The Phase III ETHOS trial results are exciting and
demonstrate that Breztri
Aerospheresignificantly reduces
the rate of exacerbations. This is also the first time we have seen
the benefit of fixed-dose triple-combination therapy at two inhaled
corticosteroid doses, which could transform treatment practice by
allowing physicians to select the optimal dose for individual
patients."
The safety and tolerability of Breztri
Aerosphere were consistent
with the known profiles of the dual comparators. In the trial, all
combination therapies were administered in a pressurised
metered-dose inhaler (pMDI) using Aerosphere delivery technology.
The ETHOS trial results will be presented at an upcoming medical
meeting. Breztri
Aerospherehas been approved in
Japan and is under regulatory review in China, where it has been
granted Priority Review by the National Medical Products
Administration. It is also under regulatory review in the US and
EU.
About ETHOS
ETHOS is a randomised, double-blinded, multi-centre,
parallel-group, 52-week trial to assess the efficacy and safety
of Breztri
Aerosphere in symptomatic
patients with moderate to very severe COPD and a history of
exacerbation(s) in the previous year.2 Outcomes
in the ETHOS trial included, as a primary endpoint, the rate of
moderate or severe exacerbations. Full trial design details are
published in Respiratory
Medicine.3
Bevespi Aerosphere is a
fixed-dose dual bronchodilator in a pMDI, combining glycopyrronium,
a long-acting muscarinic antagonist (LAMA), and
formoterol fumarate, a long-acting beta2-agonist (LABA). PT009 is a
single inhaler, fixed-dose dual-combination therapy of budesonide,
an inhaled corticosteroid (ICS), and formoterol fumarate, a LABA.
It was developed as a relevant comparator in clinical trials
for Breztri
Aerosphere.4,5
ETHOS involved more than 8,500 patients who had experienced
≥1 moderate/severe exacerbation in the previous year and were
receiving at least two inhaled maintenance treatments at entry into
the trial.2,3
About the ATHENA clinical trial programme
ATHENA is AstraZeneca's Phase III clinical trial programme
for Breztri
Aerosphere, which includes more
than 15,500 patients globally across 11 trials.2,3,4,5,6 The
four key trials are ETHOS, KRONOS, TELOS and
SOPHOS.2,3,4,5,6
KRONOS is a Phase III randomised, double-blinded, parallel-group,
24-week, chronic-dosing, multi-centre trial that assessed the
efficacy and safety of Breztri
Aerosphere. The trial
compared Breztri
Aerosphere with Bevespi
Aerosphere, Symbicort
Turbuhaler (budesonide/formoterol fumarate) and PT009.
Patients were given two inhalations twice a day
of Breztri
Aerosphere, Bevespi
Aerosphere, Symbicort
Turbuhaler or PT009.
KRONOS involved approximately 1,900 patients with moderate to very
severe COPD.6
In the KRONOS trial, Breztri Aerosphere met
six of seven primary endpoints versus dual comparators, and PT009
met two non-inferiority endpoints to support the qualification of
PT009 as an active comparator. As published
in The
Lancet Respiratory Medicine, in a key secondary
endpoint, Breztri Aerosphere showed
a statistically-significant 52% reduction in the rate of moderate
or severe COPD exacerbations compared with Bevespi
Aerosphere in a patient population
that was not required to have had an exacerbation in the previous
12 months.6 Breztri
Aerosphere also demonstrated
reductions in the rate of moderate or severe COPD exacerbations
versus PT009 and Symbicort
Turbuhaler (18%
and 17% respectively), which were numerically but not
statistically-significant improvements. The incidence of
adjudicated pneumonia was low and comparable in all treatment
arms.6 The
primary and secondary endpoints and treatment comparisons in the
KRONOS trial differed according to regional regulatory
requirements.6
About Breztri Aerosphere
Breztri Aerosphere has
been approved in Japan and is under regulatory review for approval
in China, where it has been granted Priority Review by the National
Medical Products Administration. It is also under review in the US
and EU.
Under the terms of the agreement to acquire Pearl Therapeutics
Inc., AstraZeneca anticipates making a $150m milestone payment upon
US regulatory approval of Breztri Aerosphere for COPD. This payment would be the final
development and regulatory milestone under that
agreement.
About COPD
COPD is a progressive disease which can cause obstruction of
airflow in the lungs resulting in debilitating bouts of
breathlessness.1 It
affects an estimated 384 million people worldwide and is predicted
to be the third leading cause of death by 2020.1,7 Improving
lung function, reducing exacerbations and managing daily symptoms
such as breathlessness are important treatment goals in the
management of COPD.1
About AstraZeneca in respiratory diseases
Respiratory is one of AstraZeneca's main therapy areas, and our
medicines reached more than 18 million patients as maintenance
therapy in 2018. AstraZeneca's aim is to transform asthma and COPD
treatment through inhaled combinations at the core of care,
biologics for the unmet needs of specific patient populations, and
scientific advancements in disease modification.
The Company is building on a 40-year heritage in respiratory
disease and AstraZeneca's capability in inhalation technology spans
pressurised metered-dose inhalers and dry powder inhalers, as well
as the Aerosphere delivery technology. The company also has a
growing portfolio of respiratory biologics
including Fasenra (anti-eosinophil, anti-IL-5 receptor alpha),
now approved for severe, eosinophilic asthma and in development for
severe nasal polyposis and other potential indications, and
tezepelumab (anti-TSLP), which has been granted Breakthrough
Therapy Designation by the US Food and Drug Administration in
patients with severe asthma and is in Phase III trials.
AstraZeneca's research aims at addressing underlying disease
drivers by focusing on the lung epithelium, lung immunity, lung
regeneration and neuronal functions.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that
focuses on the discovery, development and commercialisation of
prescription medicines, primarily for the treatment of diseases in
three therapy areas - Oncology, CVRM and Respiratory. AstraZeneca
operates in over 100 countries and its innovative medicines are
used by millions of patients worldwide. For more information,
please visit astrazeneca.com and
follow us on Twitter @AstraZeneca.
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References
1. GOLD. Global
Strategy for the Diagnosis, Management and Prevention of COPD,
Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019.
[Online]. Available at: http://goldcopd.org.
Last accessed: August 2019.
2.
Clinicaltrials.gov. Study to Assess the Efficacy and Safety of
PT010 Relative to PT003 and PT009 in Subjects With Moderate to Very
Severe COPD (ETHOS). [Online]. Available
at: https://clinicaltrials.gov/ct2/show/NCT02465567. Last
accessed: August 2019.
3. Rabe K, Martinez F, Ferguson
G, et
al. A Phase III study of
triple therapy with budesonide/glycopyrrolate/formoterol fumarate
metered dose inhaler 320/18/9.6µg and 160/18/9.6µg using
co-suspension delivery technology in moderate-to-severe COPD: The
ETHOS study protocol. Respir Med. 2019; Epub ahead of print
(DOI:https://doi.org/10.1016/j.rmed.2019.08.010).
4.
Clinicaltrials.gov. Study to Assess Efficacy and Safety of PT009
Compared to PT005, PT008, and Symbicort® Turbuhaler® on
Lung Function Over 24-Weeks in Subjects With Moderate to Very
Severe COPD (TELOS). [Online]. Available
at: https://clinicaltrials.gov/ct2/show/NCT02766608.
Last accessed: August 2019.
5.
Clinicaltrials.gov. A Study to Assess the Efficacy and Safety of
PT009 Compared to PT005 on COPD Exacerbations Over a 52-Week Period
in Subjects With Moderate to Very Severe COPD (SOPHOS). [Online].
Available at: https://clinicaltrials.gov/ct2/show/NCT02727660.
Last accessed: August 2019.
6. Ferguson GT, Rabe KF, Martinez
FJ, et
al. Triple combination of
budesonide/glycopyrrolate /formoterol fumarate using co-suspension
delivery technology versus dual therapies in chronic obstructive
pulmonary disease (KRONOS): a double-blind, parallel-group,
randomised controlled trial. Lancet Respir
Med. 2018; 6:
747-758.
7. Adeloye D, Chua S, Lee
C, et
al. Global Health
Epidemiology Reference Group (GHERG). Global and regional estimates
of COPD prevalence: Systematic review and
meta-analysis. J Glob
Health. 2015; 5:
020415.
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
Date:
28 August
2019
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By: /s/
Adrian Kemp
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Name:
Adrian Kemp
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Title:
Company Secretary
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