Date: 2014-01-08

Type of information: Submission of a Market Application in the US

Product name: Seebri® Breezhaler®/Enurev® Breezhaler®/ Tovanor® Breezhaler®

Compound: NVA237 (glycopyrronium bromide)

Therapeutic area: Respiratory diseases

Action mechanism:

NVA237 (glycopyrronium bromide) is a long-acting muscarinic antagonist (LAMA)

Company: Novartis (Switzerland)


once-daily treatment for chronic obstructive pulmonary disease (COPD)

Latest news:

* On January 8, 2015, Novartis announced that the New Drug Applications (NDAs) for QVA149 and NVA237 for the long-term maintenance treatment of chronic obstructive pulmonary disease (COPD) were submitted to the FDA in Q4 2014.

* On October 1, 2012, Novartis has announced that the European Commission has approved 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 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% 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). 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.

* On June 22, 2012, the European Medicines Agency (EMA) has announced that the Committee for Medicinal Products for Human Use (CHMP) has recommended approval of Seebri® Breezhaler®/Enurev® Breezhaler®/ Tovanor® Breezhaler® (glycopyrronium bromide) for the maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD). The benefits with the drug are its ability to relieve the symptoms experienced by patients with chronic obstructive pulmonary disease (COPD) in terms of lung function. The most common side effects is dry mouth; the safety profile is further characterised by other symptoms related to the anticholinergic effects, gastrointestinal effects as well as adverse reactions related to local tolerability. A pharmacovigilance plan will be implemented as part of the marketing authorisation.

* On September 27, 2011, Vectura Group announced that NVA237 (glycopyrronium bromide) has been filed by Novartis for marketing authorisation with the European Medicines Agency (EMA) under the brand-name Seebri® Breezhaler®, triggering a $5m milestone payment to Vectura.


Submission of marketing authorization application USA : 2014-12-00

Submission of marketing authorization application UE: 2011-09-27

Withdrawal of marketing authorization application USA:

Withdrawal of marketing authorization application UE:

US authorization:

UE authorization: 2012-10-01

Favourable opinion UE: 2011-06-21

Favourable opinion USA:

Orphan status USA:

Orphan status UE:

Pediatric exclusivit _USA:

Pediatric exclusivity UE:

OTC status:

Other news:

Is general: Yes