Novartis once-daily QVA149 shows superior efficacy in reducing exacerbations, improving lung function and quality of life in COPD patients

Results from the 64-week SPARK study published today in Lancet Respiratory Medicine showed that investigational once-daily dual bronchodilator QVA149 (indacaterol maleate 110 mcg / glycopyrronium 50 mcg) was more effective at reducing all chronic obstructive pulmonary disease (COPD) exacerbations compared to glycopyrronium 50 mcg and open-label (OL) tiotropium 18 mcg[1] a treatment with established efficacy in preventing exacerbations[2],[3],[4],[5]. This is the first study to evaluate the effect on exacerbations of dual bronchodilation with a fixed-dose combination of a long-acting beta2-agonist (LABA) and a long-acting muscarinic antagonist (LAMA), versus single LAMA therapies.

“We are delighted that results from SPARK demonstrated that QVA149 reduced the overall rate of exacerbations in patients with severe and very severe COPD. For physicians and their patients, these findings offer hope of a new effective treatment to prevent debilitating COPD exacerbations and improve health-related quality of life,” said Tim Wright, Global Head of Development at Novartis Pharma AG.

SPARK was a 64-week, multi-center, double-blind, parallel-group, active controlled study with the primary objective to show superiority of QVA149 (indacaterol maleate 110 mcg / glycopyrronium 50 mcg) versus glycopyrronium 50 mcg for the rate of moderate to severe COPD exacerbations in 2,224 patients with severe to very severe COPD. The key secondary objective was to show superiority of QVA149 compared with OL tiotropium 18 mcg with respect to the rate of moderate or severe COPD exacerbations during the treatment period. Patients aged >=40 years with >=1 COPD exacerbation in the year before were randomized to receive either once-daily QVA149, glycopyrronium or OL tiotropium 18 mcg[1].

The study met its primary endpoint demonstrating that QVA149 significantly reduced the rate of moderate or severe COPD exacerbations by 12% versus glycopyrronium (p=0.038). The rate of moderate or severe exacerbations was numerically lower (p=0.096) in patients on QVA149 compared to OL tiotropium 18 mcg. The rate of all (mild, moderate, and severe) exacerbations was significantly reduced by 15% with QVA149 compared to glycopyrronium (p=0.0012) and by 14% compared with OL tiotropium 18 mcg (p=0.0017). All treatments had an acceptable safety profile, and there was no meaningful difference between the treatment groups in the incidence of adverse and serious adverse event reporting[1]. Novartis has previously released the First Interpretable Results (FIR) for SPARK.

SPARK also demonstrated that the dual bronchodilator effect of QVA149 resulted in substantially improved lung function. During the 64-week study, results showed that lung function, as measured by trough FEV1 was significantly higher with QVA149 compared to glycopyrronium (p<0.0001) and OL tiotropium 18 mcg (p<0.0001) at each assessment during the treatment period.

Additionally, QVA149 showed significant differences in health-related quality of life during the study as demonstrated by lower St George’s Respiratory Questionnaire (SGRQ) total scores of QVA149 versus glycopyrronium (p<0.01), and OL tiotropium 18 mcg (p<0.05). Percentages of patients achieving the minimum clinically important (>=4 unit) improvement in SGRQ total scores were higher with QVA149 compared to glycopyrronium (p=0.055) or OL tiotropium 18 mcg (p=0.051), even up to Week 64[1].

The effective management of COPD exacerbations is very important to both patients and physicians, as exacerbations can impose a significant burden of morbidity, mortality, reduced quality of life and increased healthcare costs[6],[7]. Frequent exacerbations are linked to an accelerated decline in lung function[8],[9]and patients are also known to have a poorer quality of life[10]. Admissions to hospital due to exacerbations are increasing[11] and patients with more severe underlying disease account for around 70% of the direct medical costs of COPD[12].

Novartis is committed to addressing the unmet medical needs of COPD patients and improving their quality of life by providing innovative medicines and devices. SPARK is one of 10 studies investigating QVA149 for the treatment of COPD in the IGNITE Phase III clinical trial program, which involves more than 7,000 patients across 42 countries.

About the Novartis COPD portfolio

Onbrez® Breezhaler® (indacaterol maleate) is a LABA that offers clinically relevant 24-hour bronchodilation combined with a rapid onset of action within five minutes at first dose, as demonstrated in the INERGIZE Phase III trial program. Onbrez Breezhaler 150 mcg QD provided greater clinical benefit in terms of reduced shortness of breath, lower use of rescue medication and improved health status, compared with blinded tiotropium 18 mcg. Onbrez Breezhaleris approved in more than 100 countries around the world. It was first launched in the EU (150 mcg and 300 mcg once-daily doses) and has since received approvals in markets worldwide including Japan (Onbrez® Inhalation Capsules 150 mcg once-daily) and US (ArcaptaTM NeohalerTM 75 mcg once-daily).

Once-daily Seebri® Breezhaler® (glycopyrronium bromide) is a novel inhaled LAMA (also referred to as a long-acting anticholinergic) so far approved in EU, Japan, Canada, Australia and other countries as a maintenance bronchodilator treatment to relieve symptoms in adult patients with COPD. Glycopyrronium was exclusively licensed to Novartis in April 2005 by Vectura and its co-development partner Sosei. Phase III data from the GLOW 1, 2 and 3 studies demonstrated that glycopyrronium 50 mcg delivered rapid and significant sustained improvements in lung function (measured by mean FEV1) from the morning on Day 1 compared with placebo and sustained this for 24 hours over 52 weeks, and significantly improved exercise endurance versus placebo.

QVA149 is an investigational inhaled, once-daily, fixed-dose combination of indacaterol maleate and glycopyrronium bromide. QVA149 is being investigated for the treatment of COPD in the Phase III IGNITE clinical trial program. IGNITE is one of the largest international clinical trial programs in COPD comprising 10 studies in total* (ILLUMINATE, SHINE, BRIGHT, ENLIGHTEN, SPARK, BLAZE, ARISE, BEACON, RADIATE, LANTERN) with more than 7,000 patients across 42 countries. The first eight studies (ILLUMINATE, SHINE, BRIGHT, ENLIGHTEN, SPARK, BLAZE**, ARISE**, BEACON) have already completed in 2012. The studies are designed to investigate efficacy, safety and tolerability, lung function, exercise endurance, exacerbations, shortness of breath and quality of life.

*Total refers to all 10 IGNITE studies.

**BLAZE & ARISE were not included within the Q4 2012 filings to the EU and Japan.

Novartis continues development of respiratory products for delivery via the Breezhaler® device. This is a single-dose dry powder inhaler (SDDPI), which has low air flow resistance, making it suitable for patients with airflow limitation[13]. The Breezhaler® device allows patients to hear, feel and see that they have taken the full dose correctly[14].

About COPD

COPD is a progressive life-threatening disease that makes it hard to breathe, with symptoms that have a destructive impact on patients’ function and quality of life. It affects an estimated 210 million people worldwide[15] and is projected to be the third leading cause of death by 2020[16]. COPD is often considered to be a disease of later years, but estimates suggest that 50% of those with COPD are now less than 65 years old, resulting in increases in absenteeism, premature retirement and reductions in workforce participation[17].

References:

1. Wedzicha JA, Decramer M, Ficker JH, et al. Analysis of Chronic Obstructive Pulmonary Disease Exacerbations with the Dual Bronchodilator QVA149 Compared with Glycopyrronium and Tiotropium (SPARK): a Randomized, Double-blind, Parallel-group Study. Lancet Respir Med 2013 http://www.thelancet.com/journals/lanres/onlinefirst Accessed 23 April 2013
2. Niewoehner DE, Rice K, Cote C, et al. Prevention of exacerbations of chronic obstructive pulmonary disease with tiotropium, a once-daily inhaled anticholinergic bronchodilator: a randomized trial. Ann Intern Med 2005; 143: 317-26.
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14. SPC: EMA. 2012. Seebri Breezhaler EU Summary of Product Characteristics. [Online] 17 October 2012. Last accessed 6 February 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR__Product_Information/human/002430/WC500133769.pdf
15. Global Alliance Against Chronic Respiratory Diseases (GARD). Global surveillance, prevention and control of chronic respiratory diseases: a comprehensive approach. Available at: http://www.who.int/gard/publications/GARD%20Book%202007.pdf. Last accessed 18 April 2013.
16. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Updated 2011. http://www.goldcopd.org/guidelines-global-strategy-for-diagnosis-management.html. Last accessed 14 April 2013.
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