NVA237 Phase III Data Showed Rapid, Sustained Improvement in Lung Function and Symptom Relief Over One Year in COPD Patients

 17 May 2012•GLOW2 study showed NVA237 superior to placebo and similar to OL tiotropium in increasing lung function, improving COPD symptoms and reducing exacerbations 1,2,3

•Results demonstrated that once-daily NVA237 had rapid onset of action at first dose, sustained 24-hour bronchodilation, and was well tolerated over 52 weeks1

•NVA237 submitted for EU approval under proposed brand name Seebri® Breezhaler®; expect US filing in 2014

•COPD is predicted to be the third leading cause of death by 20204; NVA237 has the potential to provide patients an alternative choice of LAMA therapy

Chippenham, UK – 17 May 2012: Vectura Group plc (“Vectura”; LSE: VEC) confirms the information released today by Novartis that results from the pivotal Phase III GLOW2 study demonstrated that once-daily (QD) 50 mcg NVA237 (glycopyrronium bromide) was superior to placebo in improving lung function, symptom relief and quality of life, and reducing exacerbations over a one-year period1,2,3. The data will be presented at the 2012 American Thoracic Society (ATS) International Conference May 18-23, 2012 in San Francisco, CA, USA.

GLOW2 was a 52-week double-blind, placebo-controlled, parallel-group study involving 1,066 patients to assess the efficacy, safety and tolerability of NVA237 in patients with chronic obstructive pulmonary disease (COPD). Patients were randomized to one of three treatment arms, receiving either once-daily NVA237 50 mcg, placebo (double-blind), or once-daily open-label (OL) tiotropium (Spiriva® HandiHaler®*/18 mcg). Patients were also permitted to use COPD background therapy and rescue medication.

GLOW2 met its primary endpoint by demonstrating NVA237 provided superior 24-hour bronchodilation compared to placebo at 12 weeks measured by mean trough FEV1 (97 mL; p<0.001)1. At this same time point, trough FEV1 for OL tiotropium was 83 mL greater than placebo (p<0.001)1. In addition, NVA237 showed similar efficacy to OL tiotropium in patients with moderate-to-severe COPD1. NVA237 also demonstrated rapid onset of action (within five minutes after the first dose) and sustained 24-hour bronchodilation over 52 weeks1.

At Day 1, Week 26 and Week 52 of the GLOW2 study, NVA237 showed significantly improved lung function (measured by mean trough FEV1) compared with placebo (all p<0.001)1 and results were similar to those seen with OL tiotropium1. At Day 1 and Weeks 12, 26 and 52, the FEV1 area under the curve (AUC) for 0–4 hr, 0–12 hr, 12–24 hr, and 0–24 hr for NVA237 was superior to placebo (p<0.05) and numerically greater than OL tiotropium1.

The study also demonstrated that NVA237 improved COPD symptoms and quality of life and reduced exacerbations2,3 compared with placebo. NVA237 significantly reduced breathlessness (measured by the transition dyspnea index (TDI); p=0.002), improved health-related quality of life (measured by the St George’s Respiratory Questionnaire (SGRQ); p<0.001), reduced the use of rescue medication (p=0.039), and increased the percentage of days with no daytime symptoms (p<0.05) compared with placebo over 52 weeks2.

For these symptomatic and quality of life indicators, results were numerically similar to those observed with OL tiotropium over the same time period. NVA237 also significantly prolonged the time to first exacerbation and significantly reduced the rate of moderate/severe exacerbations relative to placebo over 52 weeks (p=0.001); these effects were similar to OL tiotropium (p=0.001)3.

Throughout the GLOW2 study, NVA237 was well-tolerated with a similar incidence of adverse events to placebo and OL tiotropium3. Serious adverse events were reported less frequently with NVA237 (12.6%) than with either placebo (15.4%) or OL tiotropium (15.0%)3.

Phase II clinical trial update

Results have recently been submitted for publication from the NVA237 Phase II A2208 study. This study, comparing once-daily and twice-daily dosing regimens of NVA237, met its primary endpoint by demonstrating that all treatments (12.5 mcg, 25 mcg and 50 mcg given once or twice daily and 100 mcg once daily) provided statistically significant bronchodilation over the course of the day (measured by mean trough FEV1 at Day 28) in patients with moderate-to-severe COPD compared with placebo5.

Differences in lung function (measured by FEV1 AUC0-24h) between a single daily dose of NVA237 and the same total amount given twice-daily were modest and not clinically relevant5. Throughout the study, NVA237 showed an overall good safety profile and was well-tolerated compared with placebo5. The results of A2208 are consistent with previous NVA237 studies and support once-daily dosing of 50 mcg NVA237 in patients with moderate-to-severe COPD1,2,3,7,8.

Dr Chris Blackwell, Chief Executive of Vectura, commented:

"The GLOW2 results highlight the potential for once-daily NVA237 to help patients manage their COPD symptoms and improve their quality of life. NVA237 has been submitted for approval by Novartis and we look forward to a decision from the EU regulators in the near future."

– Ends –

*Spiriva® HandiHaler® is a registered trademark by Boehringer Ingelheim Pharma Gmbh & Co. KG.

Enquiries

Vectura Group plc +44 (0)1249 667700
Chris Blackwell, Chief Executive
Anne Hyland, Chief Financial Officer
Julia Wilson, Director of Investor Relations

FTI Consulting +44 (0)20 7831 3113
Ben Atwell
Susan Quigley
Simon Conway

Notes for editors

About NVA237
Seebri® Breezhaler® (glycopyrronium bromide/NVA237) is an investigational long-acting muscarinic antagonist (LAMA) developed as a once-daily inhaled maintenance therapy for the treatment of COPD. NVA237 is expected to be one of three innovative medicines in the Novartis COPD portfolio to be delivered using the Breezhaler® Single Dose Dry Powder Inhaler, along with Onbrez® Breezhaler® (indacaterol) and investigational QVA149 (indacaterol 110 mcg/glycopyrronium bromide 50 mcg).

Phase III data from the GLOW 1, 2 and 3 studies demonstrated that NVA237 increased patients' lung function over a 24-hour period compared to placebo, with a fast onset of action at first dose, as well as improving exercise endurance1,2,3,7,8. Glycopyrronium bromide was licensed to Novartis in April 2005 by Vectura and its co-development partner Sosei. It was submitted for regulatory approval in Europe in Q3 2011 and Japan in Q4 2011, and expected US filing is the beginning of 2014.

About the NVA237/QVA149 Licence Agreement with Novartis
NVA237 was licensed to Novartis in April 2005 by Vectura and its co-development partner, Sosei. Novartis expects to launch NVA237 outside the US as a once-daily monotherapy for COPD in 2012 and as a fixed-dose combination with indacaterol, its once-daily, long-acting beta-agonist (LABA), known as QVA149, in 2013. Vectura believes that QVA149 could be the first once-daily LAMA/LABA combination to come to market for COPD. The dual activity of a muscarinic antagonist and a beta-adrenergic agonist promises to be a potent bronchodilator and, with convenient once-daily dosing as a fixed-dose combination, has the potential to improve compliance and address a large and unmet need for COPD sufferers. The first four Novartis QVA149 Phase III studies in the treatment of COPD all met their primary endpoints. The results of the SHINE, BRIGHT, ENLIGHTEN and ILLUMINATE studies, which are key components of the IGNITE program, demonstrate the potential of QVA149 in the treatment of COPD.

Novartis received European regulatory approval for Onbrez® Breezhaler® in November 2009. In March 2012, 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.

To date, Vectura has received $35m from Novartis and, under the terms of the licence, could receive up to an additional $152.5m for achievement of regulatory and commercialisation targets for both the monotherapy and the combination product. In addition, royalties on product sales will be received in the event of successful product launches.

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 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.

About Vectura
Vectura Group plc develops inhaled therapies principally for the treatment of respiratory diseases. Vectura’s main products target diseases such as asthma and chronic obstructive pulmonary disease (COPD), a growing market that is currently estimated to be worth in excess of $25bn.

Vectura has six products marketed by its partners and a portfolio of drugs in clinical and pre-clinical development, a number of which have been licensed to major pharmaceutical companies. Vectura has development collaborations and licence agreements with several pharmaceutical companies, including Novartis, Sandoz (the generics arm of Novartis), Baxter and GlaxoSmithKline (GSK).

Vectura seeks to develop certain programmes itself where this will optimise value. Vectura’s formulation and inhalation technologies are available to other pharmaceutical companies on an out-licensing basis where this complements Vectura’s business strategy. For further information, please visit Vectura’s website at www.vectura.com

Forward-looking statements
This press release contains forward-looking statements, including statements about the discovery, development and commercialisation of products. Various risks may cause Vectura’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.

References

1 Kerwin E, et al. NVA237 once daily provides rapid and sustained bronchodilation in COPD patients, with efficacy similar to tiotropium: The GLOW2 trial. [Abstract A2920: Thematic poster session B41: Monday, 21 May, 2012; 08:15–16:30].
2 Korenblat P, et al. NVA237 once daily improves dyspnea and health-related quality of life in patients with COPD: The GLOW2 trial. [Abstract A2254: Poster discussion session A101: Sunday, 20 May, 2012; 14:00–16:30].
3 Kerwin E, et al. NVA237 once daily reduces COPD exacerbations with similar rates to tiotropium: The GLOW2 trial. [Abstract A2255: Poster discussion session A101: Sunday, 20 May, 2012; 14:00–16:30].
4 Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Updated December 2011. http://www.goldcopd.org/uploads/users/files/GOLD_Report_2011_Feb21.pdf Last accessed 9 May 2012.
5 Arievich H, Overend T, Renard D, Gibbs M, Alagappan V, Banerji D. NVA237, an inhaled long-acting muscarinic antagonist: a dose-ranging study in patients with COPD. [Respir Res 2012. manuscript in preparation].
6 Bourbeau J, Bartlett SJ. Patient adherence in COPD. Thorax 2008 Sep;63(9):831-8.
7 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)
8 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. Eur Respir J 2011;38(Suppl. 55):P4497.
 

Posted: May 2012

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