PT010 Significantly Reduced Rate of Moderate or Severe COPD Exacerbations in Phase III ETHOS Trial

Trial results published in New England Journal of Medicine

WILMINGTON, Del.--(BUSINESS WIRE)--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