THARROS is the first-ever prospective trial
to investigate the potential of an inhaled triple therapy to reduce
cardiopulmonary events, a key driver of mortality, in COPD
First patients dosed in ATHLOS Phase III
trial assessing impact of BREZTRI on integrated cardiopulmonary
parameters associated with health status and survival in patients
with COPD
AstraZeneca today announced the initiation of a Phase III trial
to investigate the potential effect of triple-combination inhaled
therapy BREZTRI AEROSPHERE® (budesonide/glycopyrronium/formoterol
fumarate, or BGF) on severe cardiopulmonary outcomes, including
death*, in people with chronic obstructive pulmonary disease (COPD)
who also have elevated cardiopulmonary risk, irrespective of their
exacerbation history.1
Also, the first participants have been dosed in ATHLOS, a Phase
III trial investigating AstraZeneca’s triple therapy BGF vs.
ICS/LABA budesonide/formoterol fumarate (BFF) or placebo on
cardiopulmonary parameters including hyperinflation and exercise
endurance time, which are associated with health status and
survival.2
COPD impacts 391 million people globally.3 The disease’s
mechanisms elevate the risk of both pulmonary and cardiac events,
including severe or fatal COPD exacerbations and cardiac events,
which is termed cardiopulmonary risk.4-8 This underlying risk is
further increased after a COPD exacerbation and may remain elevated
for up to a year following an exacerbation.9-11 Just one COPD
exacerbation doubles the risk of a heart attack and increases risk
of hospitalization and cardiopulmonary-related death.5,12-14
Cardiopulmonary causes are the most common reasons for death in
patients with COPD.15,16
Fernando Martinez, MD, MS, Chief of the Division of Pulmonary
and Critical Care Medicine at Weill Cornell Medicine and New
York-Presbyterian Hospital, and International Co-ordinating
Investigator in the THARROS trial said, “The 2024 GOLD Report
highlights the treatment effect of non-pharmacologic interventions
and inhaled triple combination therapies on mortality. The Report
calls for a more proactive therapeutic approach to improve outcomes
in COPD. If positive, the THARROS trial will provide critical
evidence about the potential of single inhaler, triple combination
therapy to reduce severe cardiopulmonary events and further advance
treatment goals in COPD, including for patients with no history of
exacerbations, for whom no evidence currently exists.”
David Berg MD, MPH, Associate Physician in Cardiovascular and
Critical Care Medicine, Brigham and Women’s Hospital, Harvard
Medical School, US added: “Large outcomes trials have transformed
the management of cardiovascular diseases by enhancing our
understanding of the potentially broad impact of therapies
targeting those diseases. Current evidence already supports a
proactive treatment approach in COPD. Now THARROS is seeking to
provide first-of-its-kind evidence to support a strategy of
comprehensive cardiopulmonary risk reduction with a triple
therapy.”
Sharon Barr, Executive Vice President, BioPharmaceuticals
R&D, AstraZeneca, said: “We have an important and urgent
mission to eliminate COPD as a leading cause of death. Even
moderate COPD exacerbations are associated with increased risks of
further lung events, severe cardiovascular complications and have
been shown to contribute to patients dying. With the
first-of-its-kind THARROS study, we aim to demonstrate the
potential of triple therapy to address cardiopulmonary risk.”
BGF is approved to treat COPD in 75 countries worldwide
including the US, EU, China and Japan.
* The severe cardiopulmonary outcome measures investigated in
THARROS include death from respiratory and cardiac causes.
BREZTRI AEROSPHERE® (budesonide/glycopyrronium/formoterol
fumarate) Important Safety Information
- BREZTRI is contraindicated in patients who have a
hypersensitivity to budesonide, glycopyrrolate, formoterol
fumarate, or product excipients
- BREZTRI is not indicated for treatment of asthma. Long-acting
beta2-adrenergic agonist (LABA) monotherapy for asthma is
associated with an increased risk of asthma-related death. These
findings are considered a class effect of LABA monotherapy. When a
LABA is used in fixed-dose combination with ICS, data from large
clinical trials do not show a significant increase in the risk of
serious asthma-related events (hospitalizations, intubations,
death) compared with ICS alone. Available data do not suggest an
increased risk of death with use of LABA in patients with COPD
- BREZTRI should not be initiated in patients with acutely
deteriorating COPD, which may be a life-threatening condition
- BREZTRI is NOT a rescue inhaler. Do NOT use to relieve acute
symptoms; treat with an inhaled short-acting beta2-agonist
- BREZTRI should not be used more often than recommended; at
higher doses than recommended; or in combination with
LABA-containing medicines, due to risk of overdose. Clinically
significant cardiovascular effects and fatalities have been
reported in association with excessive use of inhaled
sympathomimetic drugs
- Oropharyngeal candidiasis has occurred in patients treated with
orally inhaled drug products containing budesonide. Advise patients
to rinse their mouths with water without swallowing after
inhalation
- Lower respiratory tract infections, including pneumonia, have
been reported following ICS. Physicians should remain vigilant for
the possible development of pneumonia in patients with COPD as the
clinical features of pneumonia and exacerbations frequently
overlap
- Due to possible immunosuppression, potential worsening of
infections could occur. Use with caution. A more serious or fatal
course of chickenpox or measles can occur in susceptible
patients
- Particular care is needed for patients transferred from
systemic corticosteroids to ICS because deaths due to adrenal
insufficiency have occurred in patients during and after transfer.
Taper patients slowly from systemic corticosteroids if transferring
to BREZTRI
- Hypercorticism and adrenal suppression may occur with regular
or very high dosage in susceptible individuals. If such changes
occur, consider appropriate therapy
- Caution should be exercised when considering the
coadministration of BREZTRI with long-term ketoconazole and other
known strong CYP3A4 Inhibitors. Adverse effects related to
increased systemic exposure to budesonide may occur
- If paradoxical bronchospasm occurs, discontinue BREZTRI
immediately and institute alternative therapy
- Anaphylaxis and other hypersensitivity reactions (eg,
angioedema, urticaria or rash) have been reported. Discontinue and
consider alternative therapy
- Use caution in patients with cardiovascular disorders,
especially coronary insufficiency, as formoterol fumarate can
produce a clinically significant cardiovascular effect in some
patients as measured by increases in pulse rate, systolic or
diastolic blood pressure, and also cardiac arrhythmias, such as
supraventricular tachycardia and extrasystoles
- Decreases in bone mineral density have been observed with
long-term administration of ICS. Assess initially and periodically
thereafter in patients at high risk for decreased bone mineral
content
- Glaucoma and cataracts may occur with long-term use of ICS.
Worsening of narrow-angle glaucoma may occur, so use with caution.
Consider referral to an ophthalmologist in patients who develop
ocular symptoms or use BREZTRI long term. Instruct patients to
contact a healthcare provider immediately if symptoms occur
- Worsening of urinary retention may occur. Use with caution in
patients with prostatic hyperplasia or bladder-neck obstruction.
Instruct patients to contact a healthcare provider immediately if
symptoms occur
- Use caution in patients with convulsive disorders,
thyrotoxicosis, diabetes mellitus, and ketoacidosis or unusually
responsive to sympathomimetic amines
- Be alert to hypokalemia or hyperglycemia
- Most common adverse reactions in a 52-week trial (incidence ≥
2%) were upper respiratory tract infection (5.7%), pneumonia
(4.6%), back pain (3.1%), oral candidiasis (3.0%), influenza
(2.9%), muscle spasms (2.8%), urinary tract infection (2.7%), cough
(2.7%), sinusitis (2.6%), and diarrhea (2.1%). In a 24-week trial,
adverse reactions (incidence ≥ 2%) were dysphonia (3.3%) and muscle
spasms (3.3%)
- BREZTRI should be administered with extreme caution to patients
being treated with monoamine oxidase inhibitors and tricyclic
antidepressants, as these may potentiate the effect of formoterol
fumarate on the cardiovascular system
- BREZTRI should be administered with caution to patients being
treated with:
- Strong cytochrome P450 3A4 inhibitors (may cause systemic
corticosteroid effects)
- Adrenergic drugs (may potentiate effects of formoterol
fumarate)
- Xanthine derivatives, steroids, or non-potassium sparing
diuretics (may potentiate hypokalemia and/or ECG changes)
- Beta-blockers (may block bronchodilatory effects of
beta-agonists and produce severe bronchospasm)
- Anticholinergic-containing drugs (may interact additively).
Avoid use with BREZTRI
- Use BREZTRI with caution in patients with hepatic impairment,
as budesonide and formoterol fumarate systemic exposure may
increase. Patients with severe hepatic disease should be closely
monitored
INDICATION
BREZTRI AEROSPHERE is indicated for the maintenance treatment of
patients with chronic obstructive pulmonary disease (COPD).
LIMITATIONS OF USE
Not indicated for the relief of acute bronchospasm or for the
treatment of asthma.
Please see full BREZTRI Prescribing
Information, including Patient
Information.
You may report side effects related to AstraZeneca
products.
Notes
COPD
COPD refers to a group of lung diseases, including chronic
bronchitis and emphysema, that cause airflow blockage and
breathing-related problems.17 Affecting an estimated 16 million
Americans, COPD is the third leading cause of death due to chronic
disease and the sixth overall leading cause of death in the
US.18,19
BREZTRI AEROSPHERE®
BREZTRI AEROSPHERE (budesonide/glycopyrronium/formoterol
fumarate) is a single-inhaler, fixed-dose triple-combination of
formoterol fumarate, a LABA, glycopyrronium bromide, a LAMA, with
budesonide, an ICS, and delivered in a pressurized metered-dose
inhaler. BREZTRI AEROSPHERE is approved to treat COPD in more than
50 countries worldwide including the US, EU, China and Japan, and
is currently being studied in Phase III trials for asthma.
THARROS
THARROS is a randomized, multi-center, double-blind,
parallel-group trial to investigate the effect of
budesonide/glycopyrronium/formoterol fumarate (BGF) on
cardiopulmonary outcomes in COPD patients. Approximately 5,000 COPD
patients with cardiopulmonary risk, aged 40-80 years old, will be
randomized to receive either fixed-dose triple combination therapy,
BGF, or a dual bronchodilator therapy glycopyrronium/formoterol
fumarate. The trial uses a novel composite endpoint combining
respiratory and cardiac outcomes: the primary endpoint in the
THARROS trial is time to first severe cardiac event, severe COPD
exacerbation, or cardiopulmonary death.1
ATHLOS
ATHLOS is a randomized, multi-center, double-blind,
three-treatment, three-period, cross-over study to investigate the
effect of budesonide/glycopyrronium/formoterol fumarate vs
budesonide/formoterol fumarate (an ICS/LABA) or placebo on isotime
inspiratory capacity (IC) and exercise endurance time in
participants with COPD who have exertional breathlessness despite
treatment with monotherapy or dual COPD maintenance therapy. This
study will include 180 patients aged 40-80 years.2
AstraZeneca in Respiratory & Immunology
Respiratory & Immunology, part of AstraZeneca
BioPharmaceuticals is a key disease area and growth driver to the
Company.
AstraZeneca is an established leader in respiratory care with a
50-year heritage and a growing portfolio of medicines in
immune-mediated diseases. The Company is committed to addressing
the vast unmet needs of these chronic, often debilitating, diseases
with a pipeline and portfolio of inhaled medicines, biologics and
new modalities aimed at previously unreachable biologic targets.
Our ambition is to deliver life-changing medicines that help
eliminate COPD as a leading cause of death, eliminate asthma
attacks and achieve clinical remission in immune-mediated
diseases.
About 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 the
Company on social media @AstraZeneca.
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