QVA149 demonstrated superior bronchodilation compared to indacaterol 150
mcg, glycopyrronium 50 mcg, salmeterol/fluticasone 50/500 mcg BID, OL tiotropium 18 mcg and placebo[1,2]
Seebri® Breezhaler® (glycopyrronium bromide) demonstrated rapid, sustained bronchodilation
and reduced exacerbations similar to OL tiotropium 18 mcg in GLOW
pooled data analysis[3,4]
TOKYO, Sept. 3, 2012 /CNW/ - Sosei Group Corporation ("Sosei"; TSE
Mothers Index: 4565) highlights that further data from the once-daily
chronic obstructive pulmonary disease (COPD) clinical trial programs
were presented today by Novartis at the European Respiratory Society
(ERS) Congress. Overall, Novartis presented 14 abstracts, including
data from the investigational QVA149 (fixed-dose combination of
indacaterol maleate / glycopyrronium bromide) IGNITE Phase III clinical
trial program, and the glycopyrronium bromide (Seebri® Breezhaler®) GLOW Phase III clinical trial program.
Among the data presented, three new studies from the investigational
QVA149 IGNITE Phase III clinical trial program (SHINE, ILLUMINATE and
ENLIGHTEN) demonstrated that QVA149 significantly improved lung
function compared to other COPD therapies[1,2,6].Data from the GLOW program showed that glycopyrronium 50 mcg once daily
provided rapid and sustained bronchodilation, and reduced exacerbations
and symptoms when compared to placebo, similar to the levels observed
with open-label (OL) tiotropium 18 mcg[3,4].
IGNITE data demonstrated the efficacy of the dual-bronchodilator QVA149
(indacaterol maleate / glycopyrronium bromide) and showed a superior
effect on lung function and patient-reported outcomes versus
SHINE met its primary endpoint by demonstrating that once-daily QVA149
110/50 mcg improved lung function as measured by trough FEV1 compared to once-daily indacaterol maleate 150 mcg (+70mL above
indacaterol alone; p<0.001) and once-daily glycopyrronium 50 mcg (+90mL
above glycopyrronium alone; p<0.001). QVA149 110/50 mcg is an investigational inhaled dry-powder fixed-dose
combination medication that provides the equivalent amount of
indacaterol as Onbrez (indacaterol maleate) 150 mcg along with
glycopyrronium 50 mcg. QVA149 was also more effective at improving lung function compared to
OL tiotropium 18 mcg (+80mL above tiotropium; p<0.001) and placebo
(+200mL; p<0.001). Mean peak FEV1 at Week 26 was also significantly higher with QVA149 compared to
placebo (+330mL, p<0.001), indacaterol 150 mcg (+120mL; p<0.001),
glycopyrronium 50 mcg (+130mL; p<0.001) and OL tiotropium 18 mcg
(+130mL; p<0.001). Mean FEV1 area under the curve (AUC) for 0-24hr at Week 26 was significantly
higher with QVA149 compared to placebo (+320mL, p<0.001), indacaterol
150 mcg (+110mL; p<0.001), glycopyrronium 50 mcg (+110mL; p<0.001) and
OL tiotropium 18 mcg (+110mL; p<0.001).
The results also showed that QVA149 improved breathlessness measured by
the transition dyspnea index or TDI (p<0.001 versus placebo; p<0.05
versus OL tiotropium 18 mcg), increased health-related quality of life
(HRQoL) measured by the St George's Respiratory Questionnaire or SGRQ
(p<0.01 versus placebo; p<0.05 versus OL tiotropium 18 mcg) and reduced
rescue medication use (p<0.001 versus both placebo and OL tiotropium 18
mcg). QVA149 was superior to indacaterol 150 mcg and glycopyrronium 50 mcg
at reducing use of rescue medication (p<0.05 and p<0.001 respectively)
and also provided numerically higher improvements in breathlessness and
HRQoL compared to indacaterol 150 mcg and glycopyrronium 50 mcg.
ILLUMINATE compared QVA149 110/50 mcg to the twice-daily LABA/ICS
salmeterol/fluticasone 50/500 mcg head-to-head over 26 weeks in
patients with COPD . The study met its primary endpoint by demonstrating that the mean FEV1 area under the curve (AUC) for 0-12hr at Week 26 was significantly
higher with QVA149 compared to salmeterol/fluticasone 50/500 mcg
(+140mL; p<0.001). Mean FEV1 AUC0-12h was also significantly higher with QVA149 versus salmeterol/fluticasone
50/500 mcg at Day 1 (+70mL; p<0.001)and Week 12 (+120mL; p<0.001). The ILLUMINATE trial also demonstrated that QVA149, in comparison to
salmeterol/fluticasone 50/500 mcg, significantly improved
breathlessness measured by TDI (p=0.003) and reduced rescue medication
use (p=0.019) over 26 weeks.
ENLIGHTEN demonstrated the efficacy of QVA149 at improving lung function
over a 52-week period by showing that QVA149 increased FEV1 and forced vital capacity (FVC) versus placebo at Day 1 and Weeks 3, 6,
12, 26, 39 and 52 (p<0.001). At Week 52, the mean difference in FEV1 compared to placebo at 60 minutes post-dose was +257mL (p<0.001).
QVA149 was generally well tolerated in the SHINE, ILLUMINATE and
ENLIGHTEN trials with an incidence of adverse events that was similar
between respective groups[1,2,6].
GLOW pooled analyses demonstrated that investigational glycopyrronium
increased lung function, improved patient outcomes compared to placebo[3,4]
Results of the first pooled analysis of GLOW1 and GLOW2 data
demonstrated that patients on glycopyrronium 50 mcg experienced rapid,
sustained and clinically meaningful bronchodilation over 52 weeks. The improvement in FEV1 was seen within five minutes after the first dose on Day 1 (+90mL at 5
minutes and +144mL at 15 minutes versus placebo; p<0.001) and was
sustained throughout the 52-week period (p<0.001 vs. placebo). FEV1 AUC for 0-4h, 0-12h, 0-24h and 12-24h for glycopyrronium 50 mcg was
statistically significantly greater than placebo (p<0.05) and
numerically greater than OL tiotropium 18 mcg (an exploratory arm in
GLOW2) when compared to placebo on Day 1 and Weeks 12, 26 and 52. When compared to placebo, glycopyrronium 50 mcg was also numerically
higher than OL tiotropium 18 mcg versus placebo at all-time points for
trough FEV1 (Day 1 and Weeks 12, 26 and 52).
The second pooled analysis of GLOW1 and GLOW2 data found that for
patients taking glycopyrronium 50 mcg, the time to first
moderate/severe exacerbation was significantly prolonged compared to
placebo at both Week 26 (hazard ratio [HR] 0.64; p<0.001) and Week 52
(HR 0.67; p<0.001). The results were comparable in patients treated with OL tiotropium 18
mcg. Glycopyrronium 50 mcg also significantly lowered the rate of
moderate/severe exacerbations versus placebo at Weeks 26 and 52 (both
rate ratio [RR] 0.66; p<0.005).
Glycopyrronium 50 mcg improved breathlessness measured by TDI (p<0.05)
and health-related quality of life measured by SGRQ (p<0.001) at Weeks
26 and 52. The results were similar to OL tiotropium 18 mcg compared to placebo.
About the study designs
SHINE was a 26 week, multicenter, randomized, double-blind, parallel-group,
placebo and active controlled pivotal trial of 2,144 patients with
moderate-to-severe COPD to assess efficacy in terms of trough FEV1. Patients were randomized to receive QVA149, indacaterol maleate 150
mcg, glycopyrronium 50 mcg, OL tiotropium 18 mcg or placebo.
ILLUMINATE was a 26 week, multi-center, randomized, double-blind, double dummy,
parallel-group study to assess the efficacy, safety and tolerability of
once-daily QVA149 compared to twice-daily fixed dose combination of
salmeterol/fluticasone 50/500 mcg in patients with moderate-to-severe
ENLIGHTEN was a 52 week, multicenter, randomized, double-blind, parallel-group,
placebo controlled pivotal trial of 339 patients with
moderate-to-severe COPD to assess the safety and tolerability of QVA149.
GLOW1 and GLOW2 were multicenter, randomized, double-blind, placebo controlled,
parallel group studies in patients with moderate-to-severe COPD. GLOW1
was a 26 week study with patients randomized to receive once-daily
glycopyrronium 50 mcg or placebo. GLOW2 was a 52 week study with
patients randomized to receive once-daily glycopyrronium 50 mcg or
placebo, and included an exploratory arm to compare the effects of
once-daily OL tiotropium 18 mcg versus placebo[3,4].
The first pooled analysis assessed the efficacy of once-daily
glycopyrronium 50 mcg versus placebo and once-daily OL tiotropium 18
mcg over 26 to 52 weeks in 1,888 patients with moderate-to-severe COPD
from clinical trials (GLOW1 and GLOW2). The second pooled analysis assessed the efficacy of once-daily
glycopyrronium 50 mcg versus placebo and once-daily OL tiotropium 18
mcg at reducing COPD exacerbations, symptoms and improving health
status over 26 to 52 weeks in 1,854 patients from clinical trials
(GLOW1 and GLOW2).
CEO of Sosei, Shinichi Tamura commented:
"We are very encouraged by the substantial body of GLOW and IGNITE data
presented at the European Respiratory Society meeting and look forward
to the approval of glycopyrronium bromide in Europe and the filing of
QVA149 in Europe and Japan."
Notes for editors
NVA237 (glycopyrronium bromide - Seebri® Breezhaler®) was licensed to Novartis in April 2005 by Sosei and its co-development
partner, Vectura. Glycopyrronium bromide is an investigational LAMA
developed as a once-daily inhaled maintenance therapy for the treatment
of COPD. 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[12-14]. In June 2012, the European Medicines Agency's Committee for Medicinal
Products for Human Use (CHMP) adopted a positive opinion for the
approval of glycopyrronium bromide in Europe under the brand name
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 with more than
7,000 patients across 42 countries[1,2,6,15-21]. 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 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
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 and is predicted to be the third leading cause of death by 2020. 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.
Sosei is an international biopharmaceutical company anchored in Japan
with a global reach. It practises a reduced risk business model by
acquiring compounds from, and bringing compounds into, Japan through
exploitation of its unique position within global markets.
For further information about Sosei, please visit http://www.sosei.com.
This press release contains forward-looking statements, including
statements about the discovery, development and commercialisation of
products. Various risks may cause Sosei's actual results to differ
materially from those expressed or implied by the forward-looking
statements, including: adverse results in clinical development
programmes; failure to obtain patent protection for inventions;
commercial limitations imposed by patents owned or controlled by third
parties; dependence upon strategic alliance partners to develop and commercialise
products and services; difficulties or delays in obtaining regulatory
approvals to market products and services resulting from development
efforts; the requirement for substantial funding to conduct research
and development and to expand commercialisation activities; and product
initiatives by competitors. As a result of these factors, prospective
investors are cautioned not to rely on any forward-looking statements. We disclaim any intention or obligation to update or revise
any forward-looking statements, whether as a result of new information,
future events or otherwise.
Bateman E et al. Benefits of dual bronchodilation with QVA149 once daily
versus placebo, indacaterol, NVA237 and tiotropium in patients with
COPD: the SHINE study. [ERS abstract 700179; Session 306; Monday
September 3, 2012; 14:45:-16:45].
Vogelmeier C et al. Once-daily QVA149 significantly improves lung
function and symptoms compared to twice-daily fluticasone/salmeterol in
COPD patients: The ILLUMINATE study. [ERS abstract 70045; Session 52;
Sunday September 2, 2012; 08:30-10:30].
Banerji D et al. Once-daily NVA237 improves lung function in COPD
patients: pooled results of the GLOW1 and GLOW2 studies. [ERS abstract
853239; Session 245; Date: September 03, 2012 Time: 12:50-14:40.
Banerji D et al. Once-daily NVA237 reduces exacerbations and improves
symptoms in COPD patients: a pooled analysis, of the GLOW1 and GLOW2
studies. [ERS abstract 853213; Session 314; Date: September 03, 2012
Mahler D et al. Effectiveness of indacaterol and tiotropium in patients
with severe dyspnoea. [ERS abstract 850630; Session 245; Date:
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Dahl R et al. QVA149 administered once daily provides significant
improvements in lung function over 1 year in patients with COPD: the
ENLIGHTEN study. [ERS abstract 853405; Session 315; Date: September 03,
2012 Time: 14:45-16:45.
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SOURCE: Sosei Group Corporation
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