Fifth QVA149 Phase III study meets primary endpoint; filing in EU and Japan by year-end
Results from Novartis' fifth QVA149 (indacaterol maleate/glycopyrronium bromide) Phase III study, SPARK, has met its primary endpoint of a reduced rate of moderate-to-severe COPD (chronic obstructive pulmonary disease) exacerbations compared with glycopyrronium bromide (NVA237, Seebri Breezhaler). SPARK is the final study intended for initial regulatory filings of QVA149 in Europe and Japan, which are expected in the fourth quarter of 2012. The US filing of QVA149 is expected at the end of 2014. To date, the first five studies of the IGNITE QVA149 Phase III trials programme have all met their primary endpoints of efficacy, safety, exercise endurance and reduction of exacerbations.
SPARK was a 64-week, multicentre, randomised, double-blind, parallel-group, active controlled study designed to evaluate the effect of QVA149 (indacaterol maleate 110mcg/glycopyrronium 50mcg) QD versus glycopyrronium 50mcg and QD open-label (OL) tiotropium 18mcg on moderate-to-severe COPD exacerbations in 2,224 patients with severe to very severe COPD. The study met its primary endpoint by demonstrating that patients treated with once-daily (QD) investigational QVA149 for 64 weeks demonstrated a clinically meaningful and statistically significant lower rate of moderate-to-severe COPD exacerbations compared with patients treated with QD glycopyrronium 50mcg (p=0.038). The study also showed that the rate of moderate-to-severe exacerbations was numerically lower (p=0.096) in patients on QVA149 compared with OL tiotropium 18mcg. A further analysis of the data demonstrated that QVA149 was statistically significantly more effective in reducing the overall rate of all exacerbations (mild, moderate and severe) compared with glycopyrronium 50mcg (p=0.001) and OL tiotropium 18mcg (p=0.002). The adverse event profile of QVA149 was similar to both glycopyrronium 50mcg and OL tiotropium 18mcg.
The management of COPD exacerbations is important to both patients and physicians, as exacerbations can impose a significant burden of morbidity, mortality, reduced quality of life and healthcare costs. Frequent exacerbations are linked to an accelerated decline in lung function and patients are also known to have a poorer quality of life. Admissions to hospital due to exacerbations are increasing and patients with more severe underlying disease account for around 70 per cent of the direct medical costs of COPD.
QVA149 is an investigational inhaled, once-daily, fixed-dose combination of the long-acting beta2-adrenergicagonist (LABA) indacaterol maleate, and the investigational long-acting muscarinic antagonist (LAMA) glycopyrronium bromide, being investigated for the treatment of COPD in the Phase III IGNITE trial programme. IGNITE is one of the largest international trial programmes in COPD comprising ten studies in total with more than 7,000 patients across 42 countries. The first five studies (ILLUMINATE, SHINE, BRIGHT, ENLIGHTEN and SPARK) have already completed in 2012, with three additional studies (BLAZE, ARISE and BEACON) expected to be completed by the end of the year. The studies are designed to investigate efficacy, safety and tolerability, exercise endurance, exacerbations, breathlessness and quality of life.