The European Commission has approved Novartis' Seebri Breezhaler (glycopyrronium bromide) 44 mcg delivered dose (equivalent to 50 mcg glycopyrronium measured dose per capsule), as a once-daily inhaled maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD). This follows the September 28 approval of once-daily Seebri (glycopyrronium bromide) Inhalation Capsules 50 mcg in Japan.

"The approval of Seebri Breezhaler in the European Union is an exciting and critical milestone that provides physicians and patients with a new once-daily COPD therapy so they have the flexibility of having the right treatment for the right patient at the right time," said David Epstein, Division Head of Novartis Pharmaceuticals. "We are proud that Novartis can deliver on our commitment to COPD patients and physicians by being the first company to offer two once-daily monotherapy bronchodilators with different modes of action, both delivered using Breezhaler devices."

The European Commission approved Seebri Breezhaler based on data from the Novartis phase III GLOW trials which demonstrated the safety and efficacy of glycopyrronium 44 mcg and involved 1,996 COPD patients who required maintenance treatment from around the world, with many in EU countries.

The GLOW trials showed that glycopyrronium, when compared to placebo, significantly improved lung function over the first four hours after morning dosing and that this benefit was sustained for 24 hours over a 52-week period. Patients on glycopyrronium demonstrated improved lung function, reduced shortness of breath, reduced exacerbations, reduced use of rescue medication, improved quality of life and improved exercise tolerance compared to placebo.

GLOW1 was a 26-week, randomized, double-blind, placebo-controlled study. The study demonstrated the clinically significant superiority of glycopyrronium versus placebo for lung function improvements at 12 weeks (primary endpoint) measured by trough FEV1 (p<0.01).

GLOW2 demonstrated a similar magnitude of effect and also showed that glycopyrronium was similar to open-label (OL) tiotropium over 52 weeks measured by improvements in trough FEV1 compared to placebo. In addition to demonstrating benefits in terms of lung function, glycopyrronium exhibited a rapid onset of action within five minutes at first dose and reduced exacerbations. Significant benefits in both breathlessness and health-related quality of life (HRQL), as measured by the Transition Dyspnea Index (TDI) and St. George's Respiratory Questionnaire (SGRQ) compared to placebo, were also demonstrated. GLOW2 was a 52-week, randomized, double-blind, placebo-controlled study with OL tiotropium 18 mcg as an active exploratory arm.

The GLOW3 study showed that after glycopyrronium was administered in the morning, patients experienced improved exercise tolerance from the first dose onward. Overall, patients treated with glycopyrronium experienced a significant 21 per cent improvement in exercise endurance versus placebo at the end of the study (day 21), with a significant 10 per cent increase from day one (both p<0.001). In all studies, glycopyrronium was shown to have an overall safety profile similar to placebo.

Seebri Breezhaler is a long-acting muscarinic antagonist (LAMA), a type of bronchodilator that is recommended in COPD global treatment strategies as maintenance therapy. Also approved in the EU for the maintenance bronchodilator treatment of airflow obstruction in adult patients with COPD is Novartis' product Onbrez Breezhaler (indacaterol maleate /150 mcg and 300 mcg once-daily doses), a long-acting beta2-adrenergic agonist (LABA).

Novartis is currently developing a fixed-dose combination of glycopyrronium and indacaterol, QVA149, which is expected to be filed in the EU and Japan by the end of 2012. In addition, Novartis is committed to continue the study of glycopyrronium bromide in further clinical trials following this approval.

Novartis is committed to addressing the unmet medical needs of COPD patients and improving their quality of life by providing innovative medicines and devices.

Onbrez Breezhaler (indacaterol maleate) is a LABA that is currently the only COPD maintenance treatment on the market to offer clinically relevant 24-hour bronchodilation combined with a rapid onset of action at first dose, as demonstrated in the INERGIZE phase III/IV trial program[5-8]. Onbrez Breezhaler is approved in more than 85 countries around the world. It was first launched in the EU (150 mcg and 300 mcg once-daily doses) and has since received approvals in markets worldwide including Japan (Onbrez Inhalation Capsules 150 mcg once-daily) and US (Arcapta Neohaler 75 mcg once-daily).

Seebri Breezhaler (glycopyrronium bromide) is a LAMA developed as a once-daily inhaled maintenance therapy for the treatment of COPD. Glycopyrronium bromide was exclusively licensed to Novartis in April 2005 by Vectura and its co-development partner Sosei. 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. The US filing for Seebri Breezhaler is expected in 2014.

QVA149 is an investigational inhaled, once-daily, fixed-dose combination of indacaterol maleate and glycopyrronium bromide. QVA149 is being investigated for the maintenance treatment of COPD in the phase III IGNITE clinical trial programme. IGNITE is one of the largest international clinical trial programmes in COPD comprising 10 studies in total with more than 7,000 patients across 42 countries. 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 inhaled 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 drug correctly.

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.

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