European Respiratory Journal publishes Phase III TELOS trial for PT009 dual combination therapy in moderate to very severe chronic obstructive pulmonary disease

16 September 2018

AstraZeneca today announced results from the Phase III TELOS trial, which investigated the efficacy and safety of PT009 (budesonide/formoterol fumarate using Aerosphere Delivery Technology in a pressurised-metered dose inhaler (pMDI)) in patients with moderate to very severe chronic obstructive pulmonary disease (COPD), regardless of whether or not they had an exacerbation in the prior year.¹ The data were presented on Sunday 16 September at the European Respiratory Society (ERS) International Congress 2018 and published in the European Respiratory Journal.

The trial compared change in lung function for two doses of PT009 (budesonide/formoterol fumarate 320/10µg or 160/10µg) to the monotherapy components (budesonide pMDI 320µg and formoterol fumarate pMDI 10µg). A non-inferiority comparison of PT009 320/10µg to open-label Symbicort Turbuhaler (budesonide/formoterol fumarate 400/12µg) was also conducted.¹ PT009 is being characterised to qualify as a relevant comparator in clinical trials for PT010, AstraZeneca’s triple combination therapy, which is also in late stage development.²

Results for the dual primary lung function endpoints (trough forced expiratory volume in one second (FEV1) and FEV1 area under the curve 0-4 hours post dose (AUC_0-4)) demonstrated:

PT009 vs. budesonide

• Both the 320/10µg and 160/10µg doses of PT009 significantly improved lung function (as measured by FEV₁ AUC_0-4) compared to budesonide at Week 24 and over 24 weeks.¹

PT009 vs. formoterol fumarate

• PT009 320/10µg resulted in significant improvements at Week 24 and over 24 weeks in trough FEV1 compared to formoterol fumarate pMDI.¹
• PT009 160/10µg achieved a numerical improvement without reaching statistical significance in lung function compared to formoterol fumarate (as measured by trough FEV1 at Week 24 and over 24 weeks).¹

PT009 vs. Symbicort Turbuhaler

• PT009 320/10µg demonstrated non-inferiority to Symbicort Turbuhaler on lung function (as measured by trough FEV1 and FEV1 AUC_0–4, over 24 weeks).¹

Dr Colin Reisner, Head of Respiratory, Global Medicines, AstraZeneca, said: “TELOS has achieved its primary objective of supporting PT009 as a suitable comparator to our fixed-dose triple combination therapy PT010, which is in late-stage development for COPD. Budesonide and formoterol fumarate are well-established medicines for the effective treatment of COPD and the TELOS results support their efficacy and safety when administered using Aerosphere Delivery Technology.”

Gary Ferguson, Professor of the Pulmonary Research Institute of Southeast Michigan, Livonia, Michigan and lead author of the TELOS trial publication, said: “The combination of budesonide and formoterol fumarate in a single inhaler is a current standard of care in COPD. The TELOS trial demonstrates that PT009 using the Aerosphere Delivery Technology is an effective maintenance treatment for patients with COPD and a suitable comparator for PT010, the investigational fixed-dose triple combination therapy.”

In the key secondary endpoint of time to first moderate to severe exacerbation, PT009 320/10µg achieved a statistically significant improvement compared to formoterol fumarate and a nominally significant improvement for PT009 160/10µg compared to formoterol fumarate. A numerical dose response favouring PT009 320/10µg over PT009 160/10µg was observed for the majority of primary and secondary efficacy endpoints, including exacerbations.

There were no new or unexpected safety or tolerability signals for PT009 in the trial. The incidence of adjudicated pneumonia in the inhaled corticosteroid (ICS) and non-ICS containing treatment arms was low and comparable: PT009 320/10µg (0.8%), PT009 160/10µg (1.1%), budesonide (0.5%) and formoterol fumarate (1.4%). The most frequently reported adverse events were nasopharyngitis, upper respiratory tract infection, COPD, hypertension, back pain, headache, cough, dyspnoea, oral candidiasis, bronchitis, sinusitis, diarrhoea, dysphonia, muscle spasms, anxiety and fatigue.¹

NOTES TO EDITORS

About COPD

Chronic obstructive pulmonary disease (COPD) is a progressive disease which can cause obstruction of airflow in the lungs resulting in debilitating bouts of breathlessness.³ It affects an estimated 384 million people worldwide⁴ and is predicted to be the third leading cause of death by 2020.³ Improving lung function, reducing exacerbations and managing daily symptoms such as breathlessness are important to the management of COPD.³

COPD exacerbations significantly impair quality of life and are linked to disease progression, accelerated decline in lung function, increased hospitalisations and mortality.⁵ Even one severe exacerbation carries an increased risk of mortality.⁶

About PT009 and the Aerosphere portfolio

PT009 is a single inhaler, fixed-dose dual combination therapy of budesonide, an inhaled corticosteroid (ICS) with formoterol fumarate, a long-acting beta2-agonist (LABA). It is being developed using AstraZeneca’s Aerosphere Delivery Technology. Aerosphere Delivery Technology is also the platform for the approved medicine Bevespi Aerosphere and for PT010 a single inhaler, fixed-dose triple combination therapy of budesonide, formoterol fumarate and glycopyrronium, a long-acting muscarinic antagonist (LAMA).

About TELOS and the ATHENA clinical trial programme

TELOS is a randomised, double-blind, parallel-group, 24-week, Phase III trial, which was conducted at 253 sites across seven countries (Canada, Czech Republic, Germany, Hungary, Poland, Russia and the US) between June 2016 and November 2017.⁷ Patients entering the trial had to be symptomatic despite treatment with one or more inhaled bronchodilators as COPD maintenance therapy for six weeks or more. The trial included symptomatic patients with moderate to very severe COPD irrespective of whether or not they had an exacerbation in the prior year.

In total, eight of the ten primary comparisons in the TELOS trial were met, including two non-inferiority comparisons between PT009 320/10µg and Symbicort Turbuhaler (see table below).¹

ATHENA is AstraZeneca’s Phase III clinical trial programme for PT010, which includes more than 15,500 patients globally across 11 trials.^7-10 The four key trials are ETHOS, KRONOS, TELOS and SOPHOS. ETHOS, TELOS and SOPHOS include low and high doses of ICS and stratification of patients by eosinophil levels as part of randomisation, for PT010 and PT009 respectively.^7,9,10

About Symbicort

Symbicort is a combination formulation containing budesonide, an ICS, and formoterol fumarate, a LABA, in a single inhaler. Symbicort is approved in approximately 120 countries to treat COPD either as Symbicort Turbuhaler or Symbicort pMDI.

About AstraZeneca in Respiratory Disease

Respiratory disease 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 2017. 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-5rɑ), now approved for severe eosinophilic asthma and in development for severe nasal polyposis, and tezepelumab (anti-TSLP), which is in Phase III trials and achieved its Phase IIb primary and secondary endpoints. AstraZeneca’s research is focused on addressing underlying disease drivers focusing on the lung epithelium, lung immunity and lung regeneration.

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, 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 www.astrazeneca.com and follow us on Twitter @AstraZeneca.

References

1.     Ferguson GT, Papi A, Anzueto A, Kerwin EM, Cappelletti C, Duncan EA, Nyberg J, Dorinsky P. Budesonide/formoterol MDI with co-suspension delivery technology in COPD – The TELOS study. Eur Respir J 2018; Sep 16. [Epub ahead of print] http://erj.ersjournals.com/user/login?destination=/content/52/3/1801334   

2.     AstraZeneca Annual Report and Form 20-F Information 2017. [Online]. Available at:   https://www.astrazeneca.com/content/dam/az/Investor_Relations/annual-report-2017/annualreport2017.pdf Last accessed: August 2018.

3.     GOLD. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2018. [Online]. Available at: http://goldcopd.org. Last accessed: August 2018.

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.     Halpin MG. D, Miravitlles M, Metzdorf N, Celli B. Impact and prevention of severe exacerbations of COPD: a review of the evidence. International Journal of COPD; 2017; 12: 2891–2908

6.     Suissa S, Dell’Aniello S, Ernst P. Long-term natural history of chronic obstructive pulmonary disease: severe exacerbations and mortality. Thorax 2012; 67 (11): 957–963

7.     Clinicaltrials.gov. Study to Assess Efficacy and Safety of PT009 Compared to PT005, PT008, and Symbicort® Turbuhaler® 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 2018.

8.     Clinicaltrials.gov. A Randomized, Double-Blind, Parallel-Group, 24-Week, Chronic-Dosing, Multi-Center Study to Assess the Efficacy and Safety of PT010, PT003, and PT009 Compared With Symbicort® Turbuhaler® (Kronos) (KRONOS). [Online]. Available at: https://clinicaltrials.gov/ct2/show/NCT02497001. Last accessed: August 2018.

9.     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 2018.

10.  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 2018.