AstraZeneca Announces Full Results from Phase III ETHOS Trial of Breztri Aerosphere in Moderate-to-Very Severe COPD

Shanghai, June 24, 2020 /PRNewswire/ -- The complete positive results from the Phase III ETHOS clinical trial of Breztri were announced today. The trial demonstrated that, in patients with moderate to very severe chronic obstructive pulmonary disease (COPD), AstraZeneca’s triple therapy Breztri^®Lingchang^®(Budesonide/Glycopyrronium/Formoterol Fumarate) Can Significantly Reduce the Incidence of Moderate-to-Severe Acute Exacerbations^[1]。

Compared with glycopyrronium/formoterol inhalation aerosol, the budesonide/glycopyrronium/formoterol fumarate treatment group demonstrated a 24% reduction in exacerbation rate (p < 0.001). Compared with PT009 budesonide/formoterol fumarate, the budesonide/glycopyrronium/formoterol fumarate treatment group showed a 13% reduction in exacerbation incidence (p = 0.003). In this trial, the two dual-therapy regimens used as controls are currently recommended treatments for COPD.^[2]。

For a key secondary endpoint, budesonide/glycopyrronium/formoterol fumarate reduced the risk of all-cause mortality by 46% compared with glycopyrronium/formoterol inhalation aerosol (unadjusted p = 0.01).^[3]。

The findings of this study were published in The New England Journal of Medicine and were also presented during the pulmonary medicine clinical trial results session of the American Thoracic Society International Conference.^[3]AstraZeneca will continue to review these data with health regulatory authorities.

Klaus Rabe, Principal Investigator of the ETHOS trial, Professor of Pulmonary Medicine at Kiel University in Germany, and Director of the Department of Respiratory Medicine at the Lung Center Grosshansdorf in Germany, stated: “The results of the Phase III ETHOS trial are significant, demonstrating that budesonide/glycopyrronium/formoterol fumarate helps reduce exacerbation rates in this progressive disease. The findings also indicate that reducing all-cause mortality risk is achievable, thereby shifting the treatment goals for chronic obstructive pulmonary disease (COPD).”

Mene Pangalos, Executive Vice President of BioPharmaceuticals R&D at AstraZeneca, stated: “Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally, and exacerbations can lead to increased patient mortality. The results from the Phase III ETHOS clinical trial once again confirm that budesonide/glycopyrronium/formoterol fumarate reduces the rate of disease exacerbations compared with dual therapy. We are excited about the data obtained regarding all-cause mortality, as this is one of the key considerations in the management of COPD.”

The safety and tolerability of budesonide/glycopyrronium/formoterol fumarate were consistent with the known profiles of the two dual therapies. In this trial, the most commonly reported adverse events were nasopharyngitis, COPD, and upper respiratory tract infection. The incidence of confirmed pneumonia was 4.2% in the budesonide/glycopyrronium/formoterol fumarate group, 2.3% in the glycopyrronium/formoterol metered-dose inhaler group, and 4.5% in the PT009 group.

The above results are based on the use of standard-dose budesonide (an inhaled corticosteroid, ICS) in the budesonide/glycopyrronium/formoterol fumarate combination (320/14.4/9.6 mcg). In this trial, the budesonide/glycopyrronium/formoterol fumarate combination with half-dose budesonide (160/14.4/9.6 mcg) also significantly reduced the rate of moderate-to-severe exacerbations compared to the control groups. The two control groups were glycopyrronium/formoterol fumarate pressurized metered-dose inhaler (14.4/9.6 mcg) and PT009 (budesonide/formoterol fumarate: 320/9.6 mcg).^[1]。

Breztri® Aerosphere® has beenJapanandChinaApproved for the treatment of COPD, and currently undergoing regulatory review in the United States and Europe.

*PT009 (budesonide/formoterol fumarate) has not been marketed globally and has not yet obtained approval for the indication of chronic obstructive pulmonary disease (COPD).

About COPD

Chronic Obstructive Pulmonary Disease (COPD) is a progressive condition that can lead to airflow obstruction in the lungs, primarily manifesting as chest tightness and shortness of breath.^[2]. It is estimated that there are 384 million patients with chronic obstructive pulmonary disease (COPD) worldwide^[4], it is the third leading cause of death worldwide^[5]. Improving lung function, reducing the risk of acute exacerbations, and alleviating daily symptoms such as dyspnea are important treatment goals for chronic obstructive pulmonary disease (COPD).^[2]. Even a single acute exacerbation of chronic obstructive pulmonary disease (COPD) can significantly accelerate the rate of decline in lung function.^[6], deterioration of quality of life^[7], which will significantly shorten the life expectancy of patients with chronic obstructive pulmonary disease (COPD) and increase the risk of mortality^[8,9]。

References

1.  Rabe KF, Martinez FJ, Ferguson GT, et al. Inhaled Triple Therapy at Two Glucocorticoid Doses in Moderate-to-Very Severe COPD. NEJM 2020; [IN PRESS]

2.  GOLD. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2020. [Online]. Available at: http://goldcopd.org. [Last accessed: June 2020]. 

3.  Rabe KF. Inhaled Triple Therapy at Two Glucocorticoid Doses in Moderate-to-Very Severe COPD: The ETHOS Study. ATS Scientific Symposium. Breaking News: Clinical Trial Results in Pulmonary Medicine. June 24, 2020. 

4.  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 (2): 020415.

5.  Quaderi SA, Hurst JR. The unmet global burden of COPD. Glob Health Epidemiol Genom. 2018; 3: e4. Published 2018 Apr 6. doi:10.1017/gheg.2018.1

6.  Halpin DMG, Decramer M, Celli BR, et al. Effect of a single exacerbation on decline in lung function in COPD. Respiratory Medicine 2017; 128: 85-91.

7.  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

8.  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.

9.  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.