Parma, Italy, October 1, 2019 – Today, Chiesi Farmaceutici an international research-focussed healthcare group (Chiesi Group), announced the results of two studies published in The Lancet concluding that a single-inhaler triple therapy with extrafine beclometasone dipropionate (inhaled corticosteroid; BDP), formoterol fumarate (long-acting β2-agonist; FF), and glycopyrronium (long-acting muscarinic antagonist; G) improves lung function and reduces exacerbations in adult patients with asthma uncontrolled on ICS/LABA therapy with a history of one or more exacerbation in the previous year. These are the first studies to evaluate the relative efficacy and safety of single-inhaler triple therapy with those of inhaled corticosteroid plus a long-acting β2-agonist in adults with asthma.
The two Phase III, 52-week studies, TRIMARAN (N=1,155) and TRIGGER (N=1,437), compared the efficacy and safety of medium-ICS dose BDP/FF/G 100/6/10 microgram (μg) versus BDP/FF 100/6 (TRIMARAN,) and high-ICS dose BDP/FF/G 200/6/10 μg versus BDP/FF 200/6 μg and BDP/FF 200/6 μg plus tiotropium 2.5 μg (TRIGGER) in adult patients with asthma uncontrolled on medium or high-dose ICS plus long-acting β2-agonist therapy (ICS/LABA). Study authors concluded that by week 26 BDP/FF/G improved pre-dose FEV1 by 57mL (95% CI 15–99; p=0.0080) and 73mL (26–120; p=0.0025) versus BDP/FF in TRIMARAN and TRIGGER, respectively, with 15% (rate ratio 0.846 [0.725–0.987]; p=0.0331) and 12% (0.880 [0.751–1.030]; p=0.1102) reductions in moderate-to-severe exacerbation rate over 52 weeks. Furthermore, in the pre-specified pooled analysis, BDP/FF/G reduced the annualized rate of severe exacerbations versus BDP/FF by 23% (p=0.0076), reduced the rate of moderate exacerbations by 12% (p=0.0427) and reduced combined moderate and severe exacerbations by 14% (p=0.0083).
Prof. J. Christian Virchow, one of the principal investigators of the TRIMARAN and TRIGGER studies, from Rostock, Germany, said, “Some patients with uncontrolled asthma are required to use two different inhalers, of different design and with different instructions for use – and often with different dosing regimens. This is not only inconvenient for patients and healthcare providers who provide instruction on correct inhaler use but can negatively impact treatment adherence and persistence, leading to poor disease control. So, these findings are exciting for patients and healthcare providers alike because they provide first time evidence of the benefits of a single-inhaler triple combination of BDP/FF/G for those with uncontrolled asthma.”
Alessandro Chiesi, Region Europe Head, Chiesi Group said, “Today’s publication in The Lancet highlights Chiesi’s commitment to providing efficacious, well-tolerated and convenient treatment options for a disease that affects 8% of adults across Europe. We are proud to be supporting these innovative studies which provide us with key evidence on the benefits of single-inhaler triple therapy over other combination inhaler therapies. We look forward to continuing to showcase the benefits that our triple therapy in a single inhaler can bring to adult patients with asthma uncontrolled on ICS/LABA therapy.”
Adverse events were reported by 410–431 (72–75%) patients with BDP/FF/G, 443–455 (77–79%) with BDP/FF and 210 (73%) with BDP/FF plus tiotropium. The majority of events were mild or moderate in severity, and few were considered related to treatment. The most common adverse event in all groups was asthma exacerbation, the occurrence of which was lower with triple therapy than with BDP/FF.
Single-inhaler triple therapy consisting of an extrafine formulation (i.e., with mass median aerodynamic diameter ,
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About the TRIMARAN and TRIGGER studies
TRIMARAN and TRIGER are two randomised, parallel-group, double-blind, active-controlled studies. Eligible patients were adults with uncontrolled asthma, history of ≥1 exacerbation, and previously treated with inhaled corticosteroid (TRIMARAN, medium-dose; TRIGGER, high-dose) plus long-acting β2-agonist. After two weeks receiving BDP/FF (TRIMARAN, 100/6μg; TRIGGER, 200/6μg), patients were randomised to 52 weeks with BDP/FF/G 100/6/10μg or BDP/FF 100/6μg, two inhalations twice-daily in TRIMARAN; and BDP/FF/G 200/6/10μg or BDP/FF 200/6μg, or open-label BDP/FF 200/6μg two inhalations twice-daily plus tiotropium 2.5μg two inhalations once-daily in TRIGGER.
Between February 2016 and May 2018, 1,155 patients in TRIMARAN received BDP/FF/G (N=579) or BDP/FF (N=576); between April 2016 and May 2018, 1,437 patients in TRIGGER received BDP/FF/G (N=573), BDP/FF (N=576) or BDP/FF plus tiotropium (N=288).
Co-primary endpoints (BDP/FF/G vs BDP/FF) were: pre-dose FEV1 at week 26; rate of moderate-to-severe exacerbations over 52 weeks. Key secondary endpoints included severe exacerbation rate over 52 weeks (using pooled data).
Asthma is a common long-term condition that can affect people of all ages and causes inflammation in the airways. The prevalence of asthma in the European Union (EU) is 8.2% in adults and 9.4% in children.2 Difficult-to-treat or severe asthma occurs in 24% of patients. The direct and indirect costs of asthma to societies are substantial. Recent calculations estimate direct costs within the EU to be nearly €20 billion, indirect costs to be €14 billion and a monetised value of DALYs lost to be €38 billion, which totals €72 billion.
About Chiesi Group
Based in Parma, Italy, Chiesi Farmaceutici is an international research-focussed Healthcare Group, with over 80 years of experience in the pharmaceutical industry, and with presence in 28 countries. Chiesi researches, develops and markets innovative drugs in the respiratory therapeutics, specialist medicine and rare disease areas. Its R&D organisation is headquartered in Parma (Italy), and integrated with 4 other key R&D groups in France, the USA, the UK, and Sweden to advance Chiesi's pre-clinical, clinical and registration programmes. Chiesi employs over 5,600 people. Chiesi Group is a certified Benefit corporation. For more information, please visit www.chiesi.com
1 Virchow J C et al. Single inhaler extrafine triple therapy in uncontrolled asthma: two randomised, double-blind, parallel group, controlled trials (TRIMARAN and TRIGGER). Lancet 2019
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