Trial results published in New England
Journal of Medicine
Full results from the positive Phase III ETHOS trial showed
AstraZeneca’s triple-combination therapy PT010
(budesonide/glycopyrronium/formoterol fumarate) demonstrated a
statistically significant reduction in the rate of moderate or
severe exacerbations compared with two dual-combination therapies
in patients with moderate to very severe chronic obstructive
pulmonary disease (COPD).
Compared with glycopyrronium/formoterol fumarate, PT010 achieved
a 24% reduction (p<0.001) in exacerbations. PT010 achieved a 13%
reduction (p=0.003) compared with PT009 (budesonide/formoterol
fumarate). The dual-combination therapies used as comparators in
the trial represent recommended therapeutic classes for the
treatment of COPD.
In a key secondary endpoint, PT010 showed a 46% reduction in the
risk of all-cause mortality compared with glycopyrronium/formoterol
fumarate (unadjusted p=0.01).
The results were published in the New England Journal of
Medicine and simultaneously presented at the American Thoracic
Society virtual Scientific Symposium, Clinical Trial Results in
Pulmonary Medicine. AstraZeneca will continue to review these data
with health authorities.
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 important and
demonstrate the benefit of PT010 in reducing the rate of
exacerbations in this progressive disease. The findings also show
that reducing risk of all-cause mortality is achievable and could
transform treatment goals in chronic obstructive pulmonary
disease.”
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, said: “Chronic obstructive pulmonary disease is the third
leading cause of death worldwide and exacerbations can contribute
to an increase in mortality in these patients. The results of the
Phase III ETHOS trial support the strong clinical profile of PT010
in reducing exacerbation rates compared with dual-combination
therapies. We are excited to have the data on all-cause mortality,
which is a key consideration for COPD management.”
The safety and tolerability of PT010 were consistent with the
known profiles of the dual comparators. In the trial, the most
frequently reported adverse events were nasopharyngitis, COPD and
upper respiratory tract infection. The incidence of confirmed
pneumonia was 4.2% with PT010, 2.3% with glycopyrronium/formoterol
fumarate and 4.5% with PT009.
These results are based on PT010 at the standard dose of
budesonide (budesonide/glycopyrronium/formoterol fumarate
320/14.4/9.6mcg), an inhaled corticosteroid (ICS). In the trial,
PT010 at half the dose of budesonide
(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
glycopyrronium/formoterol fumarate (14.4/9.6mcg) and PT009
(budesonide/formoterol fumarate 320/9.6mcg).
PT010 is approved in Japan and China for patients with COPD. It
is also under regulatory review in the US and EU.
COPD
COPD is a progressive disease which can cause obstruction of
airflow in the lungs resulting in debilitating bouts of
breathlessness. It affects an estimated 384 million people and is
the third leading cause of death globally. Improving lung function,
reducing exacerbations and managing daily symptoms such as
breathlessness are important treatment goals in the management of
COPD. Even a single COPD exacerbation may be associated with a
significant increase in the rate of decline in lung function, a
significant deterioration in quality of life, and can significantly
reduce life expectancy and increase the risk of mortality.
ETHOS and the ATHENA clinical trial program
ETHOS is a randomized, double-blinded, multi-center,
parallel-group, 52-week trial to assess the efficacy and safety of
PT010 in symptomatic patients with moderate to very severe COPD and
a history of exacerbation(s) in the previous year. Outcomes in the
ETHOS trial included, as a primary endpoint, the rate of moderate
or severe exacerbations.
Glycopyrronium/formoterol fumarate is a fixed-dose dual
bronchodilator in a pressurized metered-dose inhaler (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 ICS, and formoterol fumarate, a LABA. It
was developed as a relevant comparator in clinical trials for
PT010.
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.
ETHOS is part of AstraZeneca’s ATHENA Phase III clinical trial
program for PT010, which included more than 15,500 patients
globally across 11 trials. The results of the earlier pivotal Phase
III KRONOS trial were published in Lancet Respiratory Medicine.
ETHOS Primary and Key Secondary Endpoints
ETHOS Primary Endpoints
Endpoint
Timepoint
Comparison/results
Rate of moderate or severe COPD
exacerbations
Over 52 weeks
PT010 (320mcg budesonide dose) vs
glycopyrronium/formoterol fumarate
Significant (p<0.001)
PT010 (320mcg budesonide dose) vs
PT009
Significant (p=0.003)
PT010 (160mcg budesonide dose) vs
glycopyrronium/formoterol fumarate
Significant (p<0.001)
PT010 (160mcg budesonide dose) vs
PT009
Significant (p=0.002)
ETHOS Secondary Endpoints
Endpoint
Timepoint
Comparison/results
Time to first moderate or severe COPD
exacerbation
Over 52 weeks
PT010 (320mcg budesonide dose) vs
glycopyrronium/formoterol fumarate
Significant (p=0.004)
PT010 (320mcg budesonide dose) vs
PT009
Significant (p=0.006)
PT010 (160mcg budesonide dose) vs
glycopyrronium/formoterol fumarate
Significant (p=0.001)
PT010 (160mcg budesonide dose) vs
PT009
Significant (p=0.002)
Rate of severe COPD exacerbations
Over 52 weeks
PT010 (320mcg budesonide dose) vs
glycopyrronium/formoterol fumarate
Not significant (p=0.09)
PT010 (320mcg budesonide dose) vs
PT009
Significant (p=0.02)
PT010 (160mcg budesonide dose) vs
glycopyrronium/formoterol fumarate
Not significant (p=0.22)
PT010 (160mcg budesonide dose) vs
PT009
Not significant (p=0.06)
Time to death (all- cause mortality)
Over 52 weeks
PT010 (320mcg budesonide dose) vs
glycopyrronium/formoterol fumarate
Nominally Significant (unadjusted
p=0.01)
PT010 (320mcg budesonide dose) vs
PT009
Not significant (p=0.34)
PT010 (160mcg budesonide dose) vs
glycopyrronium/formoterol fumarate
Not significant (p=0.27)
PT010 (160mcg budesonide dose) vs
PT009
Not significant (p=0.59)
PT010
PT010 (budesonide/glycopyrronium/formoterol fumarate) is a
single-inhaler, fixed dose triple-combination of budesonide, an
ICS, with glycopyrronium, a LAMA, and formoterol fumarate, a
LABA.
Under the terms of the agreement to acquire Pearl Therapeutics
Inc., AstraZeneca anticipates making a $150m milestone payment upon
US regulatory approval of PT010 for COPD. This payment would be the
final development and regulatory milestone under that
agreement.
AstraZeneca in Respiratory & Immunology
Respiratory & Immunology is one of AstraZeneca’s three
therapy areas and is a key growth driver for the Company.
AstraZeneca is an established leader in respiratory care, and
its inhaled and biologic medicines reached more than 53 million
patients in 2019. Building on 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/NYSE: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development and commercialization of prescription medicines,
primarily for the treatment of diseases in three therapy areas -
Oncology, Cardiovascular, Renal and 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 www.astrazeneca-us.com
and follow the Company on Twitter @AstraZenecaUS.
US-40366 Last Updated 6/20
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