Vectura Group plc (“Vectura”; LSE: VEC) confirms the information released last week by Novartis, that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for Seebri® Breezhaler® (glycopyrronium /NVA237) 44 mcg delivered dose (50 mcg glycopyrronium per capsule), as a once-daily inhaled maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD). Seebri Breezhaler is a long-acting muscarinic antagonist (LAMA), a type of bronchodilator that is recommended in COPD global treatment strategies as maintenance therapy administered either alone or in combination with other treatmentsv.
Data from three of the Novartis Phase III GLOW trials informed the CHMP’s positive opinion for Seebri Breezhaler and included 1,996 COPD patients from around the world with many in EU countriesi,ii,iii,iv,vi.
Dr Chris Blackwell, Chief Executive of Vectura, commented:
“This positive opinion for Seebri Breezhaler is a significant value enhancing event for both Vectura and its co-development partner, Sosei. The drug was developed to a Phase II proof-of-concept by the two companies before being licensed to Novartis and, when approved, will offer COPD patients an alternative once-daily inhaled treatment. This innovative, once-daily therapy in the LAMA class has the potential to reduce breathlessness, increase the capacity to exercise and help improve quality of life. We look forward next to key data from Phase III studies of QVA149, the combination product of the long-acting betaagonist Indacaterol and NVA237, with filing in Europe expected in 2012.”
GLOW1 demonstrated the clinically significant superiority of Seebri versus placebo for lung function improvements at 12 weeks measured by trough FEV1 (p<0.01)i. GLOW2 demonstrated a similar magnitude of effect and also showed that Seebri was similar to openlabel (OL) tiotropium over 52 weeks measured by improvements in trough FEV1 compared to placeboii . In addition to demonstrating lung function benefits, Seebri Breezhaler exhibited a rapid onset of action within five minutes at first doseii and reduced exacerbationsiv. Significant benefits in both breathlessness and health-related quality of life, as measured by the Transition Dyspnoea Index (TDI) and St. George’s Respiratory Questionnaire (SGRQ) compared to placebo, were also demonstratediii.
The GLOW3 study showed that after Seebri Breezhaler was administered in the morning, patients experienced improved exercise tolerance from the first dose onwardvi. Overall, patients treated with Seebri Breezhaler 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)vi.
In all studies, Seebri Breezhaler was well tolerated with an incidence of adverse events similar to placeboi,ii,iii,iv,vi. The European Commission generally follows the recommendations of the CHMP and usually delivers its final decision within three months of the CHMP recommendation. Worldwide submissions and reviews of Seebri Breezhaler (glycopyrronium bromide/NVA237) are on-going. The US filing for Seebri Breezhaler is expected in 2014.
About Seebri Breezhaler
Seebri® Breezhaler® (glycopyrronium bromide/NVA237) is an investigational long-acting muscarinic antagonist (LAMA) being developed as a once-daily inhaled maintenance therapy for the treatment of COPD. It 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 endurancei,ii,iii,vii,viii. 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 (indacaterol maleate 110 mcg/glycopyrronium bromide 50 mcg), 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 endpointsvii,viii,ix,x. 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.
Onbrez® Breezhaler® (indacaterol maleate) is a long-acting beta-agonist (LABA) that is the only COPD treatment to offer clinically relevant 24-hour bronchodilation combined with a rapid onset of action at first dosexi,xii,xiii,xiv. Onbrez Breezhaler has also shown significant improvement in breathlessness scores compared to placebo and tiotropium. It 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 Arcapta™ Neohaler™. 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. Vectura is due to receive a milestone payment on approval by the European Medicines Agency of a marketing authorisation in a major European country.
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 worldwidexv and is predicted to be the third leading cause of death by 2020v. 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 responsibilitiesxvi.
i 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).
ii 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].
iii 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].
iv 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].
v Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Updated 2011.
vi 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
vii QVA149 A2303 (SHINE). Data on file, Novartis Pharma AG. ClinicalTrials.gov identifier: NCT01202188.
viii QVA149 A2307 (ENLIGHTEN). Data on file, Novartis Pharma AG. ClinicalTrials.gov identifier: NCT01120717.
ix QVA149 2305 (BRIGHT). Data on file, Novartis Pharma AG. ClinicalTrials.gov identifier: NCT01294787.
x QVA149 2313 (ILLUMINATE). Data on file, Novartis Pharma AG. ClinicalTrials.gov identifier: NCT01315249.
xi 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.
xii Dahl R, Chung KF, Buhl R, et al. Efficacy of a new once-daily long-acting inhaled _2-agonist indacaterol versus twice-daily formoterol in COPD. Thorax 2010;65(6):473-9.
xiii Kornmann O, Dahl R, Centanni S, et al. Once-daily indacaterol vs twice-daily salmeterol for COPD: a placebocontrolled comparison. Eur Respir J 2011;37:273-279.
xiv 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.
xv Global Alliance Against Chronic Respiratory Diseases (GARD). Global surveillance, prevention and control of chronic respiratory diseases: a comprehensive approach.
xvi 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.