PT010 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

WILMINGTON, Del.–(BUSINESS WIRE)–AstraZeneca today announced positive results from the Phase III ETHOS trial for triple-combination therapy PT010 in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).

At the standard budesonide dose, PT010 (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 glycopyrronium/formoterol fumarate 14.4/9.6mcg and PT009 (budesonide/formoterol fumarate 320/9.6mcg).

At half of the budesonide dose, PT010 (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 and PT009.

The dual-combination therapies used as comparators in the trial represent recommended therapeutic classes for the treatment of COPD.

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 PT010’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 PT010 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 PT010 were consistent with the known profiles of the dual comparators. In the trial, all combination therapies were administered in a pressurized metered-dose inhaler (pMDI) using AEROSPHERE^TM Delivery Technology.

The ETHOS trial results will be presented at an upcoming medical meeting. PT010 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 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. Full trial design details are published in Respiratory Medicine.

Glycopyrronium/formoterol fumarate 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 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.

About the ATHENA clinical trial program

ATHENA is AstraZeneca’s Phase III clinical trial program for PT010, which includes more than 15,500 patients globally across 11 trials. The four key trials are ETHOS, KRONOS, TELOS and SOPHOS.

KRONOS is a Phase III randomized, double-blinded, parallel-group, 24-week, chronic-dosing, multi-center trial that assessed the efficacy and safety of PT010. The trial compared PT010 with glycopyrronium/formoterol fumarate 14.4/9.6mcg pMDI, budesonide/formoterol fumarate turbuhaler 400/12mcg and PT009 (budesonide/formoterol fumarate 320/9.6mcg). Patients were given two inhalations twice a day of PT010, glycopyrronium/formoterol fumarate, budesonide/formoterol fumarate turbuhaler or PT009. KRONOS involved approximately 1,900 patients with moderate to very severe COPD.

In the KRONOS trial, PT010 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, PT010 showed a 52% reduction in the rate of moderate or severe COPD exacerbations compared with glycopyrronium/formoterol fumarate in a patient population that was not required to have had an exacerbation in the previous 12 months. PT010 also demonstrated reductions in the rate of moderate or severe COPD exacerbations versus PT009 and budesonide/formoterol fumarate 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. The primary and secondary endpoints and treatment comparisons in the KRONOS trial differed according to regional regulatory requirements.

About PT010

PT010 is a single inhaler, fixed-dose triple combination therapy of budesonide, an ICS with glycopyrronium, a LAMA, and formoterol fumarate, a LABA. It utilizes AstraZeneca’s AEROSPHERE™ Delivery Technology. AEROSPHERE™ Delivery Technology is also the platform for glycopyrronium/formoterol fumarate.

PT010 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 PT010 for COPD. This payment would be the final development and regulatory milestone under that agreement.

About COPD

COPD is a progressive disease associated mainly with tobacco smoking, air pollution or occupational exposure, which can cause obstruction of airflow in the lungs making it hard to breathe. In the United States, COPD is the fourth leading cause of death. Its prevalence in adults 18 years of age and older is 6.5 percent. An estimated 16 million people are currently diagnosed with COPD, and millions more are believed to have it but do not know it.

About AstraZeneca in respiratory diseases

Respiratory is one of AstraZeneca’s main therapy areas, and the Company has a growing portfolio of medicines that reached more than 18 million patients 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 pressurized metered-dose inhalers and dry powder inhalers, as well as the AEROSPHERE^TM Delivery Technology. The company has a growing portfolio of respiratory biologics including benralizumab (anti-eosinophil, anti-IL-5 receptor alpha), which is also in development for severe nasal polyposis and other eosinophilic conditions, and has been granted Orphan Drug Designation by the US Food and Drug Administration for eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES). Tezepelumab (anti-TSLP) has also been granted Breakthrough Therapy Designation 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 commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas – Oncology, Cardiovascular, Renal & Metabolism 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-us.com and follow us on Twitter @AstraZenecaUS.

US-32175 Last Updated 8/19

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