Novartis QVA149 Phase III Study Meets Primary Endpoint in Reducing Exacerbations in COPD Patients, Filing in EU and Japan by End of Year
• SPARK demonstrated QVA149 statistically significantly
reduced rate of moderate-to-severe exacerbations compared to
glycopyrronium 50 mcg[1]
• Study showed QVA149 statistically significantly reduced
overall exacerbation rates compared to glycopyrronium 50 mcg and
open-label tiotropium 18 mcg[1]
• SPARK is the final study of the IGNITE Phase III clinical
trial program intended for initial regulatory filings
Basel, August 30, 2012 - Novartis announced today that the fifth
QVA149 (indacaterol maleate / glycopyrronium bromide) Phase III
study, SPARK, met its primary endpoint of a reduced rate of
moderate-to-severe COPD exacerbations compared to glycopyrronium
bromide (Seebri® Breezhaler®)[1]. SPARK is the final study
intended for initial regulatory filings of QVA149 in Europe and
Japan, which are expected in Q4 2012. US filing of QVA149 is
expected at the end of 2014. To date, the first five studies of the
IGNITE QVA149 Phase III clinical trials program have all met their
primary endpoints of efficacy, safety, exercise endurance, and
reduction of exacerbations[1-5].
"We are very pleased that SPARK showed a reduction of
exacerbations, further demonstrating that QVA149 could improve the
lives of patients with COPD," said Tim Wright, Head of Development,
Novartis Pharmaceuticals. "We are looking forward to filing QVA149
initially in Europe and Japan, which will bring us another step
closer to providing a full range of innovative COPD medicines to
help physicians select the right treatment for the right patient at
the right time."
SPARK met its primary endpoint by demonstrating that patients
treated with once-daily (QD) investigational QVA149 for 64 weeks
demonstrated a clinically meaningful and statistically significant
lower rate of moderate-to-severe COPD exacerbations compared to
patients treated with QD glycopyrronium 50 mcg (p=0.038)[1]. The
study also showed that the rate of moderate-to-severe exacerbations
was numerically lower (p=0.096) in patients on QVA149 compared to
open-label (OL) tiotropium 18 mcg[1].
A further analysis of the data demonstrated that QVA149 was
statistically significantly more effective in reducing the overall
rate of all exacerbations (mild, moderate and severe) compared to
glycopyrronium 50 mcg (p=0.001) and OL tiotropium 18 mcg
(p=0.002)[1]. The adverse event (AE) profile of QVA149 was similar
to both glycopyrronium 50 mcg and OL tiotropium 18 mcg[1].
The management of COPD exacerbations is important to both patients
and physicians, as exacerbations can impose a significant burden of
morbidity, mortality, reduced quality of life and 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].
SPARK was a 64-week, multi-center, randomized, double-blind,
parallel-group, active controlled study designed to evaluate the
effect of QVA149 (indacaterol maleate 110 mcg / glycopyrronium 50
mcg) QD versus glycopyrronium 50 mcg and QD OL tiotropium 18 mcg on
moderate-to-severe COPD exacerbations in 2,224 patients with severe
to very severe COPD[1].
QVA149 is an investigational inhaled, once-daily, fixed-dose
combination of the long-acting beta2-adrenergicagonist (LABA)
indacaterol maleate, and the investigational long-acting muscarinic
antagonist (LAMA) glycopyrronium bromide, 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 with more than
7,000 patients across 42 countries[1-5],[13-20]. 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,
exercise endurance, exacerbations, breathlessness and quality of
life[1-5],[13-17].
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.
In addition to investigational QVA149, the Novartis COPD portfolio
also includes Onbrez® Breezhaler® (indacaterol maleate) and
glycopyrronium bromide (Seebri® Breezhaler®).
Onbrez® Breezhaler® (indacaterol maleate) is a QD LABA that
is currently the only COPD treatment on the market to offer
clinically relevant 24-hour bronchodilation combined with a rapid
onset of action of five minutes at first dose, as demonstrated in
the INERGIZE Phase III trial program[21-24]. Onbrez®
Breezhaler® has also shown significant improvement in
breathlessness scores compared to placebo and OL tiotropium 18
mcg[21]. Onbrez® Breezhaler® was first launched in the EU
in 150 mcg and 300 mcg once-daily doses. Most recently, Novartis
launched the 75 mcg once-daily dose in the US under the brand name
ArcaptaTM NeohalerTM. It is also available as a 150 mcg once-daily
dose in Japan under the brand name Onbrez® Inhalation
Capsules.
Glycopyrronium bromide (Seebri® Breezhaler®) is an
investigational LAMA developed as a once-daily inhaled maintenance
therapy for the treatment of COPD. Phase III data from the GLOW1, 2
and 3 studies demonstrated that glycopyrronium bromide 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[25-27]. Glycopyrronium bromide was
licensed to Novartis in April 2005 by Vectura and its
co-development partner Sosei.
All of the Novartis 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
particularly 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[18].
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[28] and is predicted to be the third leading cause of
death by 2020[29]. 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[30].
Disclaimer
The foregoing release contains forward-looking statements that can
be identified by terminology such as "intended," "expected,"
"could," "looking forward to," "will," "being investigated,"
"designed," "committed," "launched," or similar expressions, or by
express or implied discussions regarding potential regulatory
submissions or approvals for QVA149 or regarding potential future
revenues from QVA149. You should not place undue reliance on these
statements. Such forward-looking statements reflect the current
views of management regarding future events, and involve known and
unknown risks, uncertainties and other factors that may cause
actual results with QVA149 to be materially different from any
future results, performance or achievements expressed or implied by
such statements. There can be no guarantee that QVA149 will be
submitted or approved for sale in any market, or at any particular
time. Nor can there be any guarantee that QVA149 will achieve any
particular levels of revenue in the future. In particular,
management's expectations regarding QVA149 could be affected by,
among other things, unexpected clinical trial results, including
unexpected new clinical data and unexpected additional analysis of
existing clinical data; unexpected regulatory actions or delays or
government regulation generally; competition in general;
government, industry and general public pricing pressures; the
company's ability to obtain or maintain patent or other proprietary
intellectual property protection; unexpected manufacturing issues;
the impact that the foregoing factors could have on the values
attributed to the Novartis Group's assets and liabilities as
recorded in the Group's consolidated balance sheet, and other risks
and factors referred to in Novartis AG's current Form 20-F on file
with the US Securities and Exchange Commission. Should one or more
of these risks or uncertainties materialize, or should underlying
assumptions prove incorrect, actual results may vary materially
from those anticipated, believed, estimated or expected. Novartis
is providing the information in this press release as of this date
and does not undertake any obligation to update any forward-looking
statements contained in this press release as a result of new
information, future events or otherwise.
About Novartis
Novartis provides innovative healthcare solutions that address the
evolving needs of patients and societies. Headquartered in Basel,
Switzerland, Novartis offers a diversified portfolio to best meet
these needs: innovative medicines, eye care, cost-saving generic
pharmaceuticals, preventive vaccines and diagnostic tools,
over-the-counter and animal health products. Novartis is the only
global company with leading positions in these areas. In 2011, the
Group achieved net sales of USD 58.6 billion, while approximately
USD 9.6 billion (USD 9.2 billion excluding impairment and
amortization charges) was invested in R&D throughout the Group.
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http://www.novartis.com/.
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References
[1] 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 21 August 2012.
[2] 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 21 August 2012.
[3] 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 21 August 2012.
[4] 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 21 August 2012.
[5] ClinicalTrials.gov. A Study to Assess the Long-term Safety of
QVA149 (ENLIGHTEN). NCT01120717.
http://www.clinicaltrials.gov/ct2/show/NCT01120717?term=NCT01120717&rank=1.
Last accessed 21 August 2012.
[6] Simoens S et al. Clinical and economic analysis of
antimicrobial therapy of chronic obstructive pulmonary disease
exacerbations. Int J Clin Pract. 2007;61:200-206.
[7] Hurst J et al. Chronic obstructive pulmonary disease: the
clinical management of an acute exacerbation. Postgrad Med J.
2004;80:497-505.
[8] Kanner R, et al. Lower respiratory illness promote FEV1 decline
in current smokers but not ex-smokers with mild chronic obstructive
pulmonary disease. Results from the Lung Health Study. Am J Respir
Crit Care Med 2001;164:358-64.
[9] Donaldson G et al. Relationship between exacerbation frequency
and lung function decline in chronic obstructive pulmonary disease.
Thorax. 2002;57:847-52.
[10] Seemungal TAR et al. Effect of exacerbation on quality of life
in patients with chronic obstructive pulmonary disease. Am J Respir
Crit Care Med. 1998;157:1418-22.
[11] Lung and Asthma Information Agency. Trends in hospital
admissions for lung disease. Fact sheet 2001/4. London: St George's
Hospital Medical School.
[12] Sullivan S et al. The economic burden of COPD. Chest.
200;117(suppl):5S-9S.
[13] 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 21 August 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 21 August 2012.
[15] 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 22 August 2012.
[16] 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 22 August 2012.
[17] 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 22 August 2012.
[18] Onbrez® Breezhaler® (indacaterol) EU Summary of
Product Characteristics May 31, 2011
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/001114/human_med_001219.jsp&mid=WC0b01ac058001d124.
Last accessed 21 August 2012.
[19] FDA Access Data. Spiriva® HandiHaler® Medical Review
Part 2, pages 37-38.
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-395_Spiriva.cfm.
Last accessed 21 August 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 21 August 2012.
[21] 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.
[22] 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.
[23] 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.
[24] 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.
[25] 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 (7 December 2011).
[26] 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 21 August
2012.
[27] 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.
[28] 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 21 August 2012.
[29] 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 21 August 2012.
[30] 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.
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Posted: August 2012
