The Lancet publishes the results of Chiesi Farmaceutici TRILOGY study, which shows one year data on the superior efficacy of the first extrafine fixed ICS/LABA/LAMA triple combination for COPD treatment compared with standard therapy

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Date: 07/09/2016

At the Congress of the European Respiratory Society (ERS), currently taking place in London


The Lancet publishes the results of Chiesi Farmaceutici TRILOGY study, which shows one year data on the superior efficacy of the first extrafine fixed ICS/LABA/LAMA triple combination for COPD treatment compared with standard therapy


  • The results of the study provide convincing support for the first-in-class Triple inhaler for the effective long-term treatment of COPD (Chronic Obstructive Pulmonary Disease). The inhaler has been specifically formulated to deliver extrafine particles efficiently to the lung resulting in marked improvements in patient outcomes.
  • This is another achievement that puts Chiesi and its Research Centres at the cutting edge of the development of innovative therapies for the treatment of COPD.
  • The results of a second pivotal study, referred to as the TRINITY study, will also be presented during the Congress, providing evidence of the superiority of ICS/LABA/LAMA also against tiotropium.


London, September 5th 2016 – The study (TRILOGY1) published in the special ERS edition of The Lancet — one of the most prestigious international medical journals— is presented on September 3 at the ERS Congress in London. The study provided for the first time one year evidence that the extrafine fixed ICS/LABA/LAMA triple combination - developed by Chiesi - is superior to the fixed dose ICS/LABA combined therapy (one of the standard treatments for this condition) regarding a series of clinical efficacy parameters, and demonstrates a high safety profile. More specifically, the new Triple:


  • Reduces the annual incidence of exacerbations, events that are the most threatening for patients and the main cause of hospitalisation, death and high costs for the healthcare system;
  • Improves significantly pulmonary function;
  • Reduces breathlessness (dyspnoea) and improves patient’s symptom profile


Moreover, the results of a second pivotal clinical trial, named TRINITY2, will also be presented on September 5 during the congress. The study has proven the superiority of the extrafine fixed ICS/LABA/LAMA combination also compared to the LAMA tiotropium, another standard therapy for COPD.


A new gold standard of care


COPD affects the respiratory system and particularly the small airways (bronchioles) 3, areas that are usually hard to reach with drugs. Moreover, the disease presents two different characteristics: an obstructive component that limits airflow especially during expiration, and an inflammatory component, both at the proximal airways and deep lung level3. The fixed triple combination tested in the TRILOGY and TRINITY studies is the first containing three different active ingredients that improve airflow and fight inflammation:


  • the anti-inflammatory inhaled corticosteroid (ICS) beclomethasone;
  • the bronchodilator LABA (long-acting β2 agonist) formoterol;
  • the bronchodilator LAMA (long-acting muscarinic antagonist) glycopyrronium;


Hence, the triple combination achieves its beneficial effect (including reducing the risk of exacerbations) by concurrently and broadly targeting the two cardinal features of the disease.

At the same time, the proprietary formulation of extrafine particles (Modulite® technology developed by Chiesi in its Research Centre) ensures that the inhaled drug also effectively reaches and treats the small airways even in the deepest regions of the lungs4, 5.


Unmet Therapeutic needs and Chiesi’s commitment


Patients with COPD have unmet therapeutic needs, such as reducing the risk of exacerbations that  impair the quality of life, lead to hospitalisation and that may even be life-threatening6, 7, 8, 9. Indeed, the quality of life10 worsens when symptoms, such as dyspnoea and cough, get out of control, and the patient might need to be hospitalised. Moreover, COPD is a disease that gets progressively worse3 and therapy might need to be continuously intensified. This requires patients to be treated with lot of drugs that, to date, have to be taken through various inhalers. Therefore, the possibility of taking all drugs needed, reaching both central and peripheral airways, by using only one inhaler considerably simplifies the treatment of COPD patients.


 “Starting from these unmet needs, Chiesi developed an extensive research and development programme on the first extrafine ICS/LABA/LAMA triple combination, and for the first time pivotal long term clinical data clearly prove its superiority compared with the two standard therapies, ICS/LABA and LAMA, which are currently recommended as first-line therapy in symptomatic COPD patients.” Commented Stefano Petruzzelli, Chief Medical Officer and Head of Global Clinical Development, Chiesi Farmaceutici.


The TRILOGY1 study


The TRILOGY study, published in The Lancet and presented on Septermber 3 at the ERS Congress, is a phase III multicentre, controlled, and randomised, double blind clinical trial with delivery of therapy for 52 weeks. The study, which was agreed in advance with the European Medicines Agency (EMA), involved 1,368 patients from 159 study sites in 14 countries in Europe and South America.


Patients — aged over 40 years with a diagnosis of severe or very severe COPD and a recent history of at least one exacerbation — were first all treated with a fixed ICS/LABA double combination for 2 weeks and then randomised into two groups: half the patients continued the ICS/LABA therapy while the other half was treated with the fixed ICS/LABA/LAMA triple combination. Patients were assessed after 4, 12, 26, 40 and 52 weeks.


After 26 weeks of treatment, the new Chiesi fixed dose triple therapy showed the following:


  • a statistically significant increase in morning pulmonary function prior to the intake of the first daily dose; indeed, FEV1 (Forced Expiratory Volume in 1 second) was 81 mL higher, on average, compared with the ICS/LABA double combination;


  • a statistically significant increase in pulmonary function two hours after the first daily dose; in fact,  2-hour post-dose FEV1 was 117 mL higher, on average, compared with the ICS/LABA double combination, which means that the drug effect is very rapid, a crucial factor that can improve patient compliance with treatment;


  • a marked improvement of the quality of life of patients. The Saint George’s Respiratory Questionnaire (a questionnaire that is administered to assess the quality of life of people with respiratory disorders) has, in fact, proven that patients treated with the fixed triple combination have improved their score, on average, by more than 4 units, which is deemed the clinically significant threshold.

These results were confirmed at the end of the 52-week treatment period, but very interestingly, it was also shown that the annual rate of moderate and severe exacerbations was reduced by 23%. This is extremely important since exacerbations, more than any other factor, worsen the quality of life of the COPD patient, often require admission to hospital and are the main cause of death of these patients.


“The study has, therefore, provided evidence of the importance of treating severe COPD with all three active ingredients—ICS, LABA and LAMA—and that they can be administered concurrently by using just one inhaler. The efficacy of the extrafine triple combination was proven in terms of improvements both in lung function and in important clinical parameters, such as a reduction in the incidence of exacerbations of the disease,” said Alberto Papi, Professor and Chair of Respiratory Medicine and Vice President of the School of Medicine, University of Ferrara.


The TRINITY2 study  


The TRINITY study, presented on September 5 at the ERS Congress, is a controlled, randomised, double blind, multicentre trial with delivery of therapy for a total of 52 weeks. It involved 2,580 patients aged over 40 years with severe or very severe COPD, who were divided into three arms: one group was treated with tiotropium (LAMA), another group with the fixed triple combination (ICS/LABA/LAMA) and the third group with an extemporary triple therapy (ICS/LABA plus LAMA, taken separately). Results demonstrate that Chiesi’s fixed triple combination achieved the following:


  • Reduction of moderate and severe exacerbations by 20% compared to tiotropium (LAMA);


  • A statistically significant increase in morning lung function prior to the intake of the first daily dose; indeed, FEV1 (Forced Expiratory Volume in 1 second) was 61 mL higher, on average, compared with tiotropium (LAMA).


Moreover, the efficacy and safety of Chiesi’s fixed triple combination were comparable to those of the extemporary triple therapy, with the additional benefit that patients could use just one inhaler.


We are proud of the results achieved by our research and development programme and, in the course of next year, we count on providing further data that confirms the efficacy and superiority of the fixed dose ICS/LABA/LAMA therapeutic combination, which we deem is the appropriate option to treat a disease such as COPD. This option, on which Chiesi has long been working in its Research Centres, ensures a dual benefit. Indeed, on one hand it marks genuine progress in the management of patients, to reduce the impact of their pathological condition, on their health and on their quality of life.  On the other hand, importantly its clinical impact may leverage a health economic benefit because it may avoid the direct and indirect costs associated with patient hospitalisation” says Paolo Chiesi, Vice President and R&D Director of Chiesi Farmaceutici.



About COPD


COPD is a respiratory disease characterized by a persistent bronchial obstruction, associated with an increased chronic inflammatory response of the airways to noxious particles or gas. The classic symptoms associated with COPD are dyspnoea, chronic cough and chronic productive sputum. In some cases, an acute worsening of the above mentioned symptoms may occur, triggering an exacerbation. A double mechanism is at work in the bronchial obstruction in COPD patients: on one hand, an inflammation of the small airways together with the thickening of the airways walls and increased airflow resistance may occur. On the other, a progressive destruction of lung parenchyma (emphysema) associated with the loss of elastic retraction of the lung may take place. It is important to underline that both mechanisms may coexist, leading to a significant airflow reduction throughout the lungs.




1 THELANCET-D-16-04974R1, S0140-6736(16)31354-X

2 2016 ERS conference, London: Late breaking topics in airways disease: Oral presentation, Monday September 5. Room C (10:45-12.45)

3 Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease, 2016 update.

4 Gupta P.P. et al.; Singapore Med J 2009; 50 (2): 193-200

5 Studio Carverley et al. 2010

6 B. R. Celli et al., Statement ATS/ERS 2015, Eur RespirJ 2015; 45: 879 – 905 DOI: 10.1183/09031936.00009015

7 Progetto Libra 2010, Road Map BPCO, Rinite e Asma,

8 Gard Italy, Sorveglianza nell'ambito delle patologie respiratorie, 25 giugno 2015

9 Groenewegen KH, Schols AM, Wouters EF. Mortality and mortality-related factors after hospitalization for acute exacerbation of COPD. Chest 2003;124:459-67

10 P. Hernandez et al., Living with chronic obstructive pulmonary disease: A survey of patients' knowledge and attitudes, Respiratory Medicine (2009) 103, 1004-12.