Sosei Group Corporation: Data at ERS Shows Efficacy of Once-daily COPD Portfolio Versus Comparators, Further Establishes Dual-bronchodilator QVA149
TOKYO, September 3, 2012/PRNewswire-FirstCall/ --
- 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(R) Breezhaler(R) (glycopyrronium
bromide) demonstrated rapid, sustained
bronchodilation and reduced
exacerbations similar to OL tiotropium 18 mcg in GLOW
pooled data analysis[3,4]
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(R)
Breezhaler(R)) 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 comparators[1,2,6]
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)[1]. 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[7]. 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)[1]. 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)[1]. 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)[1].
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)[1]. 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[1].
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 [2]. 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)[2]. Mean
FEV1 AUC0-12h was also significantly higher with QVA149 versus
salmeterol/fluticasone 50/500 mcg at Day 1 (+70mL;
p<0.001)[2]and Week 12 (+120mL; p<0.001)[2]. 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[2].
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)[6]. At Week 52, the mean
difference in FEV1 compared to placebo at 60 minutes post-dose was
+257mL (p<0.001)[6].
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[3]. 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)[3]. 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[3]. 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)[3].
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)[4]. 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)[4].
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[4]. The results were similar to OL
tiotropium 18 mcg compared to placebo[4].
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[1]. 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 stable COPD[2].
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[6].
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)[3].
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)[4].
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
About NVA237/QVA149
NVA237 (glycopyrronium bromide - Seebri(R) Breezhaler(R)) 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 Seebri(R) Breezhaler(R).
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(R) 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(R) device allows patients to hear, feel
and see that they have taken the drug correctly[19].
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[22] and is predicted to be the third leading cause of
death by 2020[23]. 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[ 24].
About Sosei
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.
Forward-looking statements
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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
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difficulties or delays in obtaining regulatory approvals to market
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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.
References
1) Bateman E et al. Benefits of dual
bronchodilation with QVA149 once daily
versus placebo, indacaterol, NVA237
and tiotropium in patients with COPD: the SHINE
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2) Vogelmeier C et al. Once-daily QVA149
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fluticasone/salmeterol in COPD patients: The
ILLUMINATE study. [ERS abstract
70045; Session 52; Sunday September 2, 2012;
08:30-10:30].
3) Banerji D et al. Once-daily NVA237 improves
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GLOW2 studies. [ERS abstract 853239; Session 245;
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4) Banerji D et al. Once-daily NVA237 reduces
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Source: Sosei Group Corporation
Enquiries: Sosei Group Corporation, Tokyo Office, Milica
STOJKOVIC, Investor Relations, +81-(0)3-5210-3399, mstojkovic@sosei.com ; London
Office, Kathryn LYDON, PA to CEO & Corporate Communication,
+44-(0)20-7691-0983, klydon@sosei.com
Posted: September 2012
