Novartis announced yesterday that the European Commission has approved Seebri®
Breezhaler® (glycopyrronium bromide) 44 mcg delivered dose (equivalent to 50
mcg glycopyrronium measured dose per capsule), as a once-daily inhaled
maintenance bronchodilator treatment to relieve symptoms in adult patients with
chronic obstructive pulmonary disease (COPD). This follows the September 28
approval of once-daily Seebri® (glycopyrronium bromide) Inhalation Capsules 50
mcg in Japan.
"The approval of Seebri® Breezhaler® in the European Union is an
exciting and critical milestone that provides physicians and patients with a
new once-daily COPD therapy so they have the flexibility of having the right
treatment for the right patient at the right time," said David Epstein,
Division Head of Novartis Pharmaceuticals. "We are proud that Novartis can
deliver on our commitment to COPD patients and physicians by being the first
company to offer two once-daily monotherapy bronchodilators with different
modes of action, both delivered using Breezhaler devices."
The European Commission approved Seebri® Breezhaler® based on data from the
Novartis Phase III GLOW trials which demonstrated the safety and efficacy of
glycopyrronium 44 mcg and involved 1,996 COPD patients who required maintenance
treatment from around the world, with many in EU countries[1],[2],[3].
The GLOW trials showed that glycopyrronium, when compared to placebo,
significantly improved lung function over the first four hours after morning
dosing and that this benefit was sustained for 24 hours over a 52-week
period[2]. Patients on glycopyrronium demonstrated improved lung function,
reduced shortness of breath, reduced exacerbations, reduced use of rescue
medication, improved quality of life and improved exercise tolerance compared
to placebo[1],[2],[3]. GLOW1 was a 26-week, randomized, double-blind,
placebo-controlled study. The study demonstrated the clinically significant
superiority of glycopyrronium versus placebo for lung function improvements at
12 weeks (primary endpoint) measured by trough FEV1 (p<0.01)[1].
GLOW2 demonstrated a similar magnitude of effect and also showed that
glycopyrronium was similar to open-label (OL) tiotropium over 52 weeks measured
by improvements in trough FEV1 compared to placebo. In addition to
demonstrating benefits in terms of lung function, glycopyrronium exhibited a
rapid onset of action within five minutes at first dose and reduced
exacerbations. Significant benefits in both breathlessness and health-related
quality of life (HRQL), as measured by the Transition Dyspnea Index (TDI) and
St. George's Respiratory Questionnaire (SGRQ) compared to placebo, were also
demonstrated. GLOW2 was a 52-week, randomized, double-blind, placebo-controlled
study with OL tiotropium 18 mcg as an active exploratory arm.[2]
The GLOW3 study showed that after glycopyrronium was administered in the
morning, patients experienced improved exercise tolerance from the first dose
onward. Overall, patients treated with glycopyrronium experienced a significant
21% improvement in exercise endurance versus placebo at the end of the study
(day 21), with a significant 10% increase from day one (both p<0.001). In
all studies, glycopyrronium was shown to have an overall safety profile similar
to placebo[3].
Seebri® Breezhaler® is a long-acting muscarinic antagonist (LAMA), a type
of bronchodilator that is recommended in COPD global treatment strategies as
maintenance therapy. Also approved in the EU for the maintenance bronchodilator
treatment of airflow obstruction in adult patients with COPD is Novartis'
product Onbrez® Breezhaler® (indacaterol maleate /150 mcg and 300 mcg
once-daily doses), a long-acting beta2-adrenergic agonist (LABA)[4].
Novartis is currently developing a fixed-dose combination of glycopyrronium
and indacaterol, QVA149, which is expected to be filed in the EU and Japan by
the end of 2012. In addition, Novartis is committed to continue the study of
glycopyrronium bromide in further clinical trials following this approval.
About the Novartis COPD portfolio
Novartis is committed to addressing the unmet medical needs of COPD patients and improving their quality of life by providing innovative medicines and devices.
Onbrez® Breezhaler® (indacaterol maleate) is a LABA that is currently the
only COPD maintenance treatment on the market to offer clinically relevant
24-hour bronchodilation combined with a rapid onset of action at first dose, as
demonstrated in the INERGIZE Phase III/IV trial program[5-8]. Onbrez®
Breezhaler® is approved in more than 85 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).
Seebri® Breezhaler® (glycopyrronium bromide) is a LAMA developed as a
once-daily inhaled maintenance therapy for the treatment of COPD. Glycopyrronium
bromide 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 increased patients' lung function over a
24-hour period compared to placebo with a fast onset of action at first dose,
and improved exercise endurance versus placebo[1],[2],[3]. The US filing for
Seebri® Breezhaler® is expected in 2014.
QVA149 is an investigational inhaled, once-daily, fixed-dose combination of
indacaterol maleate and glycopyrronium bromide. QVA149 is being investigated
for the maintenance 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 with more than 7,000 patients across 42
countries[4],[9-20]. The first five studies (ILLUMINATE, SHINE, BRIGHT,
ENLIGHTEN, SPARK) have already completed in 2012 with three additional studies
(BLAZE, ARISE, BEACON) expected to complete by the end of the year. The studies
are designed to investigate efficacy, safety and tolerability, lung function,
exercise endurance, exacerbations, breathlessness and quality of life. Initial
filings for regulatory approval are expected in Q4 2012 for Europe and Japan.
US filing is expected at the end of 2014.
All Novartis inhaled COPD portfolio products are being developed for
delivery via the Breezhaler® device, a single-dose dry powder inhaler (SDDPI),
which has low air flow resistance, making it suitable for patients with airflow
limitation, such as COPD patients. The Breezhaler® device allows patients to
hear, feel and see that they have taken the drug correctly[4].
About COPD
COPD is a progressive disease associated mainly with tobacco smoking, air pollution or occupational exposure, which can cause obstruction of airflow in the lungs resulting in debilitating bouts of breathlessness. It affects an estimated 210 million people worldwide[21] and is predicted to be the third leading cause of death by 2020[22]. Although COPD is often thought of as a disease of the elderly, 50% of patients are estimated to be within the ages of 50 and 65, which means that half of the COPD population are likely to be impacted at the peak of their earning power and family responsibilities[23].
References
1. 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.
2. Kerwin E, et al. Efficacy and safety of NVA237 versus placebo and tiotropium in patients with moderate-to-severe COPD over 52 weeks: The GLOW2 study. Eur Resp J. 2012. Published on July 26, 2012 (doi:10.1183/09031936.00040712). Last accessed 12 September 2012.
3. Beeh K, Drollmann A, Di Scala L, Smith R. 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.
4. Onbrez® Breezhaler® (indacaterol) EU Summary of Product Characteristics. Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/001114/human_med_001219.jsp&mid=WC0b01ac058001d124. Last Accessed 12 September 2012.
5. Donohue JF, Fogarty C, Lötvall J, et al. Once-daily bronchodilators for chronic obstructive pulmonary disease: Indacaterol versus tiotropium. Am J Respir Crit Care Med 2010;182:155-162.
6. Dahl R, Chung KF, Buhl R, et al. Efficacy of a new once-daily long-acting inhaled beta2-agonist indacaterol versus twice-daily formoterol in COPD. Thorax 2010;65(6):473-9.
7. Kornmann O, Dahl R, Centanni S, et al. Once-daily indacaterol vs twice-daily salmeterol for COPD: a placebo-controlled comparison. Eur Respir J 2011;37:273-279.
8. Balint B, Watz H, Amos C, et al. Onset of action of indacaterol in patients with COPD: Comparison with salbutamol and salmeterol-fluticasone. Int J Chron Obstruct Pulmon Dis 2010;5:311-318.
9. ClinicalTrials.gov. A Study to Assess the Efficacy, Safety and Tolerability of Once-daily QVA149 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) (SHINE). NCT01202188. http://www.clinicaltrials.gov/ct2/show/NCT01202188?term=NCT01202188&rank=1. Last accessed 12 September 2012.
10. ClinicalTrials.gov. QVA149 versus Fluticasone/Salmeterol in Patients With Chronic Obstructive Pulmonary Disease (COPD) (ILLUMINATE). NCT01315249 http://www.clinicaltrials.gov/ct2/show/NCT01315249?term=NCT01315249&rank=1. Last accessed 12 September 2012.
11. ClinicalTrials.gov. A Study to Assess the Long-term Safety of QVA149 (ENLIGHTEN). NCT01120717 http://www.clinicaltrials.gov/ct2/show/NCT01120717?term=QVA149+ENLIGHTEN&rank=1. Last accessed 12 September 2012
12. ClinicalTrials.gov. Effect of QVA149 on Exercise Tolerance in Patients With Chronic Obstructive Pulmonary Disease (COPD) (BRIGHT). NCT01294787. http://www.clinicaltrials.gov/ct2/show/NCT01294787?term=NCT01294787.&rank=1. Last accessed 12 September 2012.
13. ClinicalTrials.gov. Effect of QVA149 Versus NVA237 and Tiotropium on Chronic Obstructive Pulmonary Disorder (COPD) Exacerbations (SPARK). NCT01120691. http://www.clinicaltrials.gov/ct2/show/NCT01120691?term=NCT01120691.&rank=1. Last accessed 12 September 2012.
14. ClinicalTrials.gov. Long Term Safety and Tolerability of QVA149 Versus Tiotropium in Japanese Patients With Chronic Obstructive Pulmonary Disease (COPD) (ARISE). NCT01285492. http://www.clinicaltrials.gov/ct2/show/NCT01285492?term=NCT01285492.&rank=1. Last accessed 12 September 2012.
15. ClinicalTrials.gov. The Effect of QVA149 on Dyspnea in Patients With Chronic Obstructive Pulmonary Disease (COPD) (BLAZE). NCT01490125. http://www.clinicaltrials.gov/ct2/show/NCT01490125?term=NCT01490125.&rank=1. Last accessed 12 September 2012
16. ClinicalTrials.gov. 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). http://www.clinicaltrials.gov/ct2/show/NCT01529632?term=BEACON&rank=6. Last accessed 12 September 2012.
17. ClinicalTrials.gov. 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 (GLISTEN). http://www.clinicaltrials.gov/ct2/show/NCT01610037?term=GLISTEN&rank=1. Last accessed 12 September 2012.
18. ClinicalTrials.gov. The Effect of QVA149 on Health Related Quality of Life in Patients With Chronic Obstructive Pulmonary Disease (COPD) (QUANTIFY). http://clinicaltrials.gov/ct2/show/NCT01574651?term=QUANTIFY&rank=1. Last accessed 12 September 2012.
19. FDA Access Data. Spiriva Medical Review Part 2, pages 37-38.http://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-395_Spiriva.cfm. Last accessed 12 September 2012
20. FDA Access Data. Advair Medical Review Nov. 17, 2003, Page 133. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/021077_S003_ADVAIR_DISKUS.pdf Last accessed 12 September 2012.
21. 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 12 September 2012.
22. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Updated 2011.
23. Fletcher MJ et al., COPD Uncovered: An International survey on the impact of chronic obstructive pulmonary disease (COPD) on a working age population. BMC Public Health 2011;11:612.
2. Kerwin E, et al. Efficacy and safety of NVA237 versus placebo and tiotropium in patients with moderate-to-severe COPD over 52 weeks: The GLOW2 study. Eur Resp J. 2012. Published on July 26, 2012 (doi:10.1183/09031936.00040712). Last accessed 12 September 2012.
3. Beeh K, Drollmann A, Di Scala L, Smith R. 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.
4. Onbrez® Breezhaler® (indacaterol) EU Summary of Product Characteristics. Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/001114/human_med_001219.jsp&mid=WC0b01ac058001d124. Last Accessed 12 September 2012.
5. Donohue JF, Fogarty C, Lötvall J, et al. Once-daily bronchodilators for chronic obstructive pulmonary disease: Indacaterol versus tiotropium. Am J Respir Crit Care Med 2010;182:155-162.
6. Dahl R, Chung KF, Buhl R, et al. Efficacy of a new once-daily long-acting inhaled beta2-agonist indacaterol versus twice-daily formoterol in COPD. Thorax 2010;65(6):473-9.
7. Kornmann O, Dahl R, Centanni S, et al. Once-daily indacaterol vs twice-daily salmeterol for COPD: a placebo-controlled comparison. Eur Respir J 2011;37:273-279.
8. Balint B, Watz H, Amos C, et al. Onset of action of indacaterol in patients with COPD: Comparison with salbutamol and salmeterol-fluticasone. Int J Chron Obstruct Pulmon Dis 2010;5:311-318.
9. ClinicalTrials.gov. A Study to Assess the Efficacy, Safety and Tolerability of Once-daily QVA149 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) (SHINE). NCT01202188. http://www.clinicaltrials.gov/ct2/show/NCT01202188?term=NCT01202188&rank=1. Last accessed 12 September 2012.
10. ClinicalTrials.gov. QVA149 versus Fluticasone/Salmeterol in Patients With Chronic Obstructive Pulmonary Disease (COPD) (ILLUMINATE). NCT01315249 http://www.clinicaltrials.gov/ct2/show/NCT01315249?term=NCT01315249&rank=1. Last accessed 12 September 2012.
11. ClinicalTrials.gov. A Study to Assess the Long-term Safety of QVA149 (ENLIGHTEN). NCT01120717 http://www.clinicaltrials.gov/ct2/show/NCT01120717?term=QVA149+ENLIGHTEN&rank=1. Last accessed 12 September 2012
12. ClinicalTrials.gov. Effect of QVA149 on Exercise Tolerance in Patients With Chronic Obstructive Pulmonary Disease (COPD) (BRIGHT). NCT01294787. http://www.clinicaltrials.gov/ct2/show/NCT01294787?term=NCT01294787.&rank=1. Last accessed 12 September 2012.
13. ClinicalTrials.gov. Effect of QVA149 Versus NVA237 and Tiotropium on Chronic Obstructive Pulmonary Disorder (COPD) Exacerbations (SPARK). NCT01120691. http://www.clinicaltrials.gov/ct2/show/NCT01120691?term=NCT01120691.&rank=1. Last accessed 12 September 2012.
14. ClinicalTrials.gov. Long Term Safety and Tolerability of QVA149 Versus Tiotropium in Japanese Patients With Chronic Obstructive Pulmonary Disease (COPD) (ARISE). NCT01285492. http://www.clinicaltrials.gov/ct2/show/NCT01285492?term=NCT01285492.&rank=1. Last accessed 12 September 2012.
15. ClinicalTrials.gov. The Effect of QVA149 on Dyspnea in Patients With Chronic Obstructive Pulmonary Disease (COPD) (BLAZE). NCT01490125. http://www.clinicaltrials.gov/ct2/show/NCT01490125?term=NCT01490125.&rank=1. Last accessed 12 September 2012
16. ClinicalTrials.gov. 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). http://www.clinicaltrials.gov/ct2/show/NCT01529632?term=BEACON&rank=6. Last accessed 12 September 2012.
17. ClinicalTrials.gov. 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 (GLISTEN). http://www.clinicaltrials.gov/ct2/show/NCT01610037?term=GLISTEN&rank=1. Last accessed 12 September 2012.
18. ClinicalTrials.gov. The Effect of QVA149 on Health Related Quality of Life in Patients With Chronic Obstructive Pulmonary Disease (COPD) (QUANTIFY). http://clinicaltrials.gov/ct2/show/NCT01574651?term=QUANTIFY&rank=1. Last accessed 12 September 2012.
19. FDA Access Data. Spiriva Medical Review Part 2, pages 37-38.http://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-395_Spiriva.cfm. Last accessed 12 September 2012
20. FDA Access Data. Advair Medical Review Nov. 17, 2003, Page 133. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/021077_S003_ADVAIR_DISKUS.pdf Last accessed 12 September 2012.
21. 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 12 September 2012.
22. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Updated 2011.
23. Fletcher MJ et al., COPD Uncovered: An International survey on the impact of chronic obstructive pulmonary disease (COPD) on a working age population. BMC Public Health 2011;11:612.