In guidelines issued in 2011, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommended that long-acting bronchodilators are the preferred option, either alone or in combination with an inhaled corticosteroid (ICS), for maintenance treatment of patients with all but the lowest risk category of chronic obstructive pulmonary disease (COPD). Although the use of ICS should be reserved for those patients at high risk (group C and D), defined by a history of frequent exacerbations or severe airflow limitation, there is evidence that they are used widely (and possibly inappropriately) in patients with more moderate disease.
QVA149 is a once-daily inhaled fixed-dose combination therapy under development for the treatment of COPD. It combines indacaterol (a long-acting β2-agonist [LABA]) with glycopyrronium (a long-acting muscarinic antagonist [LAMA]) as a dual bronchodilator. The purpose of the current study was to see whether use of this dual bronchodilator as maintenance treatment is safe and offers any benefits compared with the common practice of using a combined LABA and ICS (salmeterol–fluticasone [SFC]; twice a day), in patients who are largely low-risk but symptomatic (moderate-to-severe [GOLD stage II-III] COPD and no history of exacerbations in the previous year).
The study randomised 523 patients to once-daily QVA149 110/50 mcg or twice-daily SFC 50/500 mcg for 26 weeks. The primary endpoint was to demonstrate the superiority of QVA149 compared with SFC for the standardised area under the curve from 0 to 12 h post dose for forced expiratory volume in 1 second (FEV1 AUC0—12h) after 26 weeks of treatment (assessed in all randomised patients who received at least one dose of study drug), which was achieved (treatment difference of 0.138 L; 95% CI 0.100-0.176; p<0.0001). QVA149 also resulted in significantly greater improvements in lung function, as well as in dyspnoea and rescue medication use, but not in disease-specific health-related quality of life. The study was not designed to assess exacerbations.
The author of a related Comment article notes that these findings are important, as LABA-ICS combination therapy is frequently prescribed for patients with moderate COPD (although not recommended), instead of a non-fixed LABA-LAMA combination (which is recommended as a second choice). However the relative efficacy of these treatments in patients with a history of exacerbations in the previous year was not addressed in this study and needs to be addressed in future trials [the SPARK study is investigating this in more severe, exacerbating patients where ICS are currently recommended]. Furthermore, since some patients with severe COPD might not respond adequately to dual therapy with either a LABA-LAMA or LABA-ICS combination, further studies are warranted to assess the efficacy and safety of triple LABA-LAMA-ICS combinations compared with dual combination therapy, for which only scant data currently exist.
The authors conclude that once-daily QVA149 shows the potential of dual bronchodilation as a future treatment option for symptomatic patients with COPD. Their results support the GOLD 2011 strategy recommendation of using one or more long-acting bronchodilators without an inhaled corticosteroid in the management of symptomatic COPD patients at low risk for exacerbations.
Novartis is expecting to file for a marketing authorisation of QVA149 in the fourth quarter of 2013/first quarter 2014. Currently in the UK, the constituents of QVA149 (glycopyrronium and indacaterol) are licensed as a maintenance bronchodilator treatment to relieve symptoms in adult patients with COPD. Neither product is on the NICE work programme.
The glycopyrronium bromide inhaler was the topic of a recent NICE evidence summary (see link below), which concluded that more robust evidence comparing patient-orientated outcomes with other active treatments for COPD would enable its place in therapy to be more clearly established.