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Press Release

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

Chiesi
Posted on: 05 Sep 16
  • The results of the study provide support for the triple combination inhaler for the effective long-term treatment of COPD (Chronic Obstructive Pulmonary Disease). The inhaler has been specifically formulated to deliver extrafine particles to the lung.
  • This is another achievement that puts Chiesi and its Research Centres at the forefront in 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 LAMA alone.

London, September 3, 2016 – The study (TRILOGY1) published in the special ERS edition of The Lancet — one of the most prestigious international medical journals— is also presented on September 4 at the ERS Congress in London. The study provided for the first time one year evidence that an extrafine formulation of a 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 an acceptable safety profile. More specifically compared to the ICS/LABA dual combination, the new triple fixed combination:

  • Reduces the annual incidence of exacerbations, events that are the most threatening for patients and the main cause of hospitalisation and even death resulting in 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 an extrafine formulation of a fixed ICS/LABA/LAMA combination compared to the LAMA alone, another standard therapy for COPD.

A new standard of care

COPD affects the respiratory system and particularly the small airways (bronchioles) 3. 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 extrafine formulation of a 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) beclometasone;
  • the bronchodilator formoterol, a LABA (a long-acting β2 agonist);
  • the bronchodilator glycopyrronium, a LAMA (long-acting muscarinic antagonist);

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.

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-threatening4, 5, 6, 7. Indeed, the quality of life8 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, 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 formulation of a ICS/LABA/LAMA triple combination, and for the first time pivotal long term clinical data clearly prove its superiority compared with 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 September 4 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 on dual 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 formulation of the 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 an 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 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 Chiesi Farmaceutici

Headquartered in Parma, Italy Chiesi Farmaceutici is an international research-focused Healthcare group, with over 80 years of experience in the pharmaceutical industry. Chiesi researches, develops and markets innovative drugs in the respiratory therapeutics, specialist medicine and rare diseases areas. Its R&D centres in Parma (Italy), Paris (France), Cary (USA), Chippenham (UK) and the R&D team of the acquired Danish company Zymenex, integrate their efforts to advance Chiesi's pre-clinical, clinical and registration programs. Chiesi employs over 4,500 people, 560 of whom are solely dedicated to R&D activities. For more information, please visit www.chiesi.com

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.

References

1.      Singh D, Papi A, Corradi M, Montagna I, Francisco C, Cohuet G, Vezzoli S, Scuri M, and Vestbo J.. Single inhaler triple therapy versus inhaled corticosteroid plus long-acting β2 agonist for chronic obstructive pulmonary disease (TRILOGY): a double-blind, parallel group, randomised controlled trial. Accepted (2016) THELANCET-D-16-04974R1, S0140-6736(16)31354-X

2.      Singh D, Corradi M, Montagna I, Cohuet G, Francisco C, Vezzoli S, Muraro A, Petruzzelli S, Scuri M, and Vestbo J. TRINITY: A phase III study to compare the efficacy and safety of an extrafine triple combination of beclometasone dipropionate (BDP), formoterol fumarate (FF), and glycopyrronium bromide (GB) pMDI (CHF5993) with tiotropium (Tio) and a free triple combination of BDP/FF (Foster®) + Tio in COPD patients. Accepted 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, Progetto Mondiale BPCO, aggiornamento 2016 (www.goldcopd.org).

4.      Celli BR et al., An official American Thoracic Society/European Respiratory Society statement: research questions in COPD. Eur Respir J 2015; 45: 879 – 905

5.      Progetto Libra 2010, Road Map BPCO, Rinite e Asma. www.goldcopd.it

6.      Gard Italy: Sorveglianza nell'ambito delle patologie respiratorie, 25 giugno 2015

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

8.      Hernandez P, Balter M, Bourbeau J, Hodder R. Living with chronic obstructive pulmonary disease: A survey of patients' knowledge and attitudes. Respiratory Medicine (2009) 103, 1004-12.

# # #

Media Contacts:

Valentina Biagini

Group Communication Manager

Chiesi Farmaceutici

+39 348 7693 623

v.biagini@chiesi.com

Rita Martins

Munro and Forster

+44 (0) 207 089 6104

+44 (0) 781 786 4815

rita.martins@munroforster.com

Brian Gunson

Munro and Forster

+44 (0) 207 089 6102

+44 (0) 771 088 1645

brian.gunson@munroforster.com

 

 

Editor's Details

Chiesi
rita.martins@munroforster.com

Last updated on: 05/09/2016

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