Once-daily glycopyrronium via the Breezhaler® device for the treatment of COPD: pharmacological and clinical profile

Abstract

In the management of chronic obstructive pulmonary disease (COPD), there is an unmet medical need for effective bronchodilator treatments that not only have a fast onset of action, but also a long duration of action and are delivered using a simple, easy-to-use device. Long-acting muscarinic antagonists such as glycopyrronium and tiotropium, along with long-acting beta-2 agonists such as indacaterol, formoterol and salmeterol are the pillars of pharmacological therapy for the long-term management of patients with COPD. Glycopyrronium, the quaternary ammonium ion of glycopyrronium bromide, acts as a competitive antagonist by selectively binding to the muscarinic receptors in the bronchial smooth musculature, thus inhibiting acetylcholine-mediated bronchoconstriction. Glycopyrronium is an inhaled once-daily long-acting muscarinic antagonist recently approved for the maintenance treatment of patients with COPD. Glycopyrronium is administered by a single-dose, dry-powder inhaler, the Breezhaler® device, designed specifically to have a low internal resistance, be easy to use and confirm efficient drug delivery in patients with a wide range of COPD severities, irrespective of the age. Glycopyrronium has been shown to provide rapid and sustained improvements in lung function, dyspnea, health status, exercise endurance and exacerbation risk and an acceptable safety and tolerability profile.

Keywords::

• bronchodilators
• chronic obstructive pulmonary disease
• glycopyrronium
• long-acting muscarinic antagonists
• muscarinic antagonists

Financial & competing interests disclosure

M Molimard has received financial support for attending meetings and fees for speaking and consulting from BMS, GSK, Mundipharma, Novartis, Pfizer and Stallergen. P D'Andrea is an employee of Novartis Pharma, AG. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

The authors were assisted in the preparation of the manuscript by Bhumika Gurnani and Mark Fedele, Novartis.

Key issues

• • Effective management of chronic obstructive pulmonary disease requires long-term therapy with agents that target one or more of the key pathophysiologic factors contributing to the symptoms and severity of the disease.

• • The challenge is to deliver a well-tolerated, effective therapy with a fast onset and long duration of action in an easy-to-use inhaler device requiring minimal inspiratory effort.

• • According to GOLD 2013 strategy document, ICS/LABA has been used inappropriately in all severities of patients.

• • The rapid onset of action of glycopyrronium following the first dose on day 1 of treatment was sustained up to 1 year of treatment.

• • Glycopyrronium is currently being developed with indacaterol as a dual bronchodilator (QVA149), to allow for more intensive therapy in patients in GOLD groups B, C and D, as recommended by the GOLD 2013 strategy. This will have the auxiliary benefit of using the same Breezhaler® device when stepping up of treatment is required in cases of progression of chronic obstructive pulmonary disease.

Notice of corrections

Since the original online publication of this article (28 August 2013), a number of small corrections have been made to the text, mostly regarding reference numbers and figure permissions. The original publication was also missing the Financial & competing interests section. This is the final version of the article.