TIDMAZN
RNS Number : 3734K
AstraZeneca PLC
28 August 2019
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's ability 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 Aerosphere significantly 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 Aerosphere has 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 320/18/9.6ug and 160/18/9.6ug 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(R) Turbuhaler(R) 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.
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