Trixeo Aerosphere receives positive CHMP opinion
19 October 2020 07:00 BST
Trixeo Aerosphere recommended for approval in the EU
by CHMP for the maintenance treatment of COPD
Recommendation of triple-combination therapy based on
positive results from ETHOS and KRONOS Phase III trials
AstraZeneca's Trixeo Aerosphere (formoterol fumarate/glycopyrronium bromide/budesonide) has been recommended for marketing authorisation in the European Union (EU) for maintenance treatment in adult patients with moderate to severe chronic obstructive pulmonary disease (COPD) who are not adequately treated by a combination of an inhaled corticosteroid (ICS) and long-acting beta2-agonist (LABA), or a combination of a LABA and a long-acting muscarinic antagonist.
Trixeo Aerosphere, a triple-combination therapy, is approved under the brand name Breztri Aerosphere in Japan, China and the US for patients with COPD.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency based its positive opinion on results from the ETHOS Phase III trial in which Trixeo Aerosphere showed a statistically significant reduction in the rate of moderate or severe exacerbations compared with dual-combination therapies Bevespi Aerosphere (glycopyrronium/formoterol fumarate) and PT009 (budesonide/formoterol fumarate) over 52 weeks.1
The recommendation for approval was also supported by data from the KRONOS Phase III trial.2 In both trials, the safety and tolerability of Trixeo Aerosphere were consistent with the profiles of the dual comparators.1,2
Klaus Rabe, Professor of Pulmonary Medicine at the University of Kiel, Director of the Department of Pneumology at Clinic Grosshansdorf, Germany, Lead Investigator of the ETHOS trial and National Co-ordinating Investigator of the KRONOS Phase III trial, said: "Preventing exacerbations is central to the management of chronic obstructive pulmonary disease, as exacerbations may cause irreversible damage and disease progression. The triple-combination therapy, Trixeo Aerosphere, has demonstrated significant benefits in reducing moderate or severe exacerbations in patients suffering from this debilitating disease."
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: "Chronic obstructive pulmonary disease is now the third leading cause of death globally and affects approximately one in 10 adults over the age of 40 in Europe. Trixeo Aerosphere has demonstrated strong clinical benefit when compared with dual-combination therapies and this positive recommendation brings us closer to providing a much-needed new treatment to patients in Europe."
COPD is a progressive disease which can cause obstruction of airflow in the lungs resulting in debilitating bouts of breathlessness.3,4,5 It affects an estimated 384 million people6 and is the third leading cause of death globally.7 In Europe, approximately 10% of adults over the age of 40 have COPD.8 Improving lung function, reducing exacerbations and managing daily symptoms such as breathlessness are important treatment goals in the management of COPD.3 A single COPD exacerbation can have a negative impact on lung function,9,10 quality of life11 and increase the risk of hospitalisation.12 Additionally, even one COPD exacerbation that results in hospitalisation increases the risk of death.13,14
ATHENA clinical trial programme
The ETHOS and KRONOS Phase III trials are part of AstraZeneca's ATHENA Phase III clinical trial programme for Trixeo Aerosphere, which included more than 15,500 patients globally across 11 trials.
ETHOS is a randomised, double-blinded, multi-centre, parallel-group, 52-week Phase III trial to assess the efficacy and safety of Trixeo Aerosphere in symptomatic patients with moderate to very severe COPD and a history of exacerbation(s) in the previous year. The primary endpoint was the rate of moderate or severe exacerbations.1 Results were published in The New England Journal of Medicine.1
KRONOS is a randomised, double-blinded, parallel-group, 24-week, chronic-dosing, multi-centre Phase III trial to assess the efficacy and safety of Trixeo Aerosphere in patients with moderate to very severe COPD regardless of whether or not they had an exacerbation in the previous year. The primary endpoints were lung function parameters.2 Results were published in The Lancet Respiratory Medicine.2
Trixeo Aerosphere (formoterol fumarate/glycopyrronium bromide/budesonide) 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 pressurised metered-dose inhaler.
Trixeo Aerosphere is approved under the brand name Breztri Aerosphere in Japan, China and the US for patients with COPD.
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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 rheumatology (including systemic lupus erythematosus), dermatology, gastroenterology, and systemic eosinophilic-driven diseases. AstraZeneca's ambition in immunology is to achieve disease control and ultimately clinical remission in targeted immune-driven diseases.
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2. 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.
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8. European lung white book. 2013. Chapter 13 Chronic obstructive pulmonary disease. Available at: https://www.erswhitebook.org/chapters/chronic-obstructive-pulmonary-disease/ [Last accessed: October 2020].
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11. Roche N, Wedzicha JA, Patalano F, et al. COPD exacerbations significantly impact quality of life as measured by SGRQ-C total score: results from the FLAME study. Eur Resp J. 2017; 50 (Suppl 61): OA1487.
12. Rothnie KJ, Müllerová H, Smeeth L, Quint JK. Natural History of Chronic Obstructive Pulmonary Disease Exacerbations in a General Practice-based Population with Chronic Obstructive Pulmonary Disease. Am Jour of Resp Crit Care Med. 2018; 198 (4): 464-471.
13. Ho TW, Tsai YJ, Ruan SY, et al. In-Hospital and One-Year Mortality and Their Predictors in Patients Hospitalized for First-Ever Chronic Obstructive Pulmonary Disease Exacerbations: A Nationwide Population-Based Study. PLOS ONE. 2014; 9 (12): e114866.
14. Suissa S, Dell'Aniello S, Ernst P. Long-term natural history of chronic obstructive pulmonary disease: severe exacerbations and mortality. Thorax. 2012; 67 (11): 957-63.
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