First in class once-daily dual bronchodilator Ultibro Inhalation Capsules (QVA149) approved for the treatment of COPD in Japan
Once-daily Ultibro® Inhalation Capsules (QVA149) (glycopyrronium / indacaterol), delivered through the Breezhaler® device, approved for relief of various symptoms due to airway obstruction in COPD
IGNITE data showed QVA149 significantly improved lung function and patient reported outcomes including breathlessness and rescue medication use, compared to current standards of care1-3
QVA149 significantly reduced the rate of all COPD exacerbations compared to glycopyrronium 50 mcg and open-label tiotropium 18 mcg3
Tokyo, Japan – 20 September 2013: Sosei Group Corporation (“Sosei”; TSE Mothers Index: 4565) confirms that the Japanese Ministry of Health, Labour and Welfare (MHLW) approved once-daily Ultibro® Inhalation Capsules (glycopyrronium 50 mcg / indacaterol 110 mcg), delivered through the Breezhaler® device, for relief of various symptoms due to airway obstruction in chronic obstructive pulmonary disease (COPD). Ultibro Inhalation Capsules were developed by Novartis under the name of QVA149 and will be available to the 5.3 million Japanese patients who may be living with COPD4. The approval triggers a $2.5m milestone payment to Sosei.
Dual bronchodilation with QVA149 is expected to set a new standard of care in COPD by combining the proven efficacy and safety benefits of two established Novartis COPD treatments, the LABA*, Onbrez® Inhalation Capsules (indacaterol), and the LAMA**, Seebri® Inhalation Capsules (glycopyrronium bromide). Both these components are delivered through the Breezhaler® device, as is QVA149, and are widely available in many countries around the world including Japan.
The efficacy and safety of QVA149 is supported by the comprehensive IGNITE Phase III clinical trial program, one of the largest international trial programs in COPD comprising 11 studies in total with more than 10,000 patients from 52 countries1-3,5-14.
From the eight IGNITE studies which completed in 20121-3,5-9, data showed that QVA149 significantly improved lung function versus several current standard treatments1,3,5 and showed significant symptomatic improvements versus placebo in breathlessness, exercise tolerance, rescue medication use and health-related quality of life1,2,5. QVA149 also demonstrated statistically significant symptomatic improvements in breathlessness, rescue medication use and health-related quality of life compared to open-label (OL) tiotropium 18 mcg1. The rate of all COPD exacerbations (mild, moderate and severe) was significantly improved with QVA149 compared to glycopyrronium 50 mcg and OL tiotropium 18 mcg3.
In clinical studies, QVA149 demonstrated an acceptable safety profile with no meaningful differences between the treatment groups (placebo, indacaterol 150 mcg, glycopyrronium 50 mcg, OL tiotropium 18 mcg, salmeterol / fluticasone (SFC) 50 mcg / 500 mcg) in the incidence of adverse and serious adverse events1-3,5. The safety profile was characterized by typical anticholinergic and beta-adrenergic effects related to the individual components of the combination1-3,5-9.
In July, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for approval of QVA149. US submission is anticipated at the end of 2014.
Ultibro®, Seebri®, Onbrez® and Breezhaler® are registered trademarks of Novartis AG.
* a long-acting beta2-adrenergic agonist, ** a long-acting muscarinic antagonist
1. Bateman ED, Feruson GT, Barnes N et al. Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study. European Respiratory Journal [Published on May 30 2013]. doi: http://dx.doi.org/10.1183/09031936.00200212. [Accessed 12 September 2013].
2. Vogelmeier C et al. Efficacy and safety of once-daily QVA149 compared with twice-daily salmeterol/fluticasone in patients with COPD (ILLUMINATE): a randomised, double-blind, parallel group study. Lancet Respiratory Medicine. 2013;1(1): 51-60.
3. Wedzicha JA 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 Respiratory Medicine 2013;1(3): 199-209.
4. Fukuchi, et al. The Nippon COPD Epidemiology (NICE) Study. Respirology 2004.
5. Beeh K et al. QVA149 once daily improves exercise tolerance and lung function in patients with COPD: the BRIGHT study. Thorax. 2012;67(2) A147.
6. Dahl R et al. Safety and efficacy of dual bronchodilation with QVA149 in COPD patients: the ENLIGHTEN study. Respiratory Medicine Journal 2013;107:1558-1567.
7. Mahler D et al. Superior lung function with once-daily QVA149 translates into improvements in patient reported breathlessness compared with placebo and tiotropium in COPD patients: the BLAZE study. [ATS abstract 45308; Session C20; Date: May 21, 2013 Time: 8:15-10:45].
8. ClinicalTrials.gov, n.d. Long Term Safety and Tolerability of QVA149 Versus Tiotropium in Japanese Patients With Chronic Obstructive Pulmonary Disease (COPD) (ARISE). [Online] Available at: http://www.clinicaltrials.gov/ct2/show/NCT01285492?term=%28ARISE%29&rank=4. [Accessed 12 September 2013].
9. ClinicalTrials.gov, n.d. Comparison of Safety and Efficacy of the Combination Product QVA149A Against the Concurrent Administration of the Individual Components, QAB149 and NVA237, in Patients With Chronic Obstructive Pulmonary Disease (COPD) (BEACON). [Online] Available at: www.clinicaltrials.gov/ct2/show/NCT01529632?term=BEACON&rank=6. [Accessed 12 September 2013].
10. ClinicalTrials.gov, n.d. Comparison of Long-term Safety of the Combination Product QVA149A Against Placebo and Standard of Care Treatment in Chronic Obstructive Pulmonary Disease Patients With Moderate to Severe Airflow Limitation (RADIATE). [Online] Available at: www.clinicaltrials.gov/ct2/show/NCT01610037?term=GLISTEN&rank=1. [Accessed 12 September 2013].
11. ClinicalTrials.gov, n.d. A 26-week Treatment Randomized, Double-blind, Double Dummy, Parallel-group Study to Assess the Efficacy, Safety and Tolerability of QVA149 (Indacaterol / Glycopyrronium Bromide) Compared to Fluticasone/Salmeterol in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease. [Online]. Available at: www.clinicaltrials.gov/ct2/show/NCT01709903?id=01709903&rank=1. [Accessed 12 September 2013].
12. ClinicalTrial.gov, n.d. A 52-week Treatment, Multi-center, Randomized, Double-blind, Double Dummy, Parallel-group, Active Controlled Study to Compare the Effect of QVA149 (Indacaterol Maleate / Glycopyrronium Bromide) With Salmeterol/Futicasone on the Rate of Exacerbations in Subjects With Moderate to Very Severe COPD (FLAME). [Online] Available at: http://clinicaltrials.gov/ct2/show/NCT01782326?term=COPD+novartis+52&rank=2. [Accessed 12 September 2013].
13. FDA Access Data, n.d.Spiriva Medical Review Part 2. [Online] Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-395_Spiriva.cfm. [Accessed 12 September 2013].
14. FDA Access Data, 2003.Advair Medical Review. [Online] Available at: www.accessdata.fda.gov/drugsatfda_docs/nda/2003/021077_S003_ADVAIR_DISKUS.pdf. [Accessed 12 September 2013].
15. EMA. 2012. Seebri Breezhaler EU Summary of Product Characteristics. [Online] 17 October 2012. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR__Product_Information/human/002430/WC500133769.pdf. [Accessed 2 August 2013].
16. D'Urzo A et al. Efficacy and safety of once-daily NVA237 in patients with moderate-to-severe COPD: the GLOW1 trial. Respiratory Research 2011;12:156.
17. Kerwin E et al. Efficacy and safety of NVA237 versus placebo and tiotropium in patients with COPD: The GLOW2 study. Eur Resp J 2012;40(5):1106-1114.
18. Beeh K et al. Once-daily NVA237 improves exercise endurance from first dose in patients with COPD: the GLOW3 trial. Int J Chron Obstruct Pulmon Dis 2012;7:503-513. 19. Pavkov et al. Characteristics of a capsule based dry powder inhaler for the delivery of indacaterol. CMRO 2010; 26; 11:2527–2533. doi:10.1185/03007995.2010.518916. 20. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Updated 2013. http://www.goldcopd.org/guidelines-globalstrategy-for-diagnosis-management.html. [Accessed 12 September 2013].
21. Patient Study 2008. Ministry of Health, Labor and Welfare.