Date: 2012-05-17
Type of information: Initiation of preclinical development
phase: 3
Announcement: Results
These results are included in the following abstracts:
• Kerwin E, et al. NVA237 once daily provides rapid and sustained bronchodilation in COPD patients, with efficacy similar to tiotropium: The GLOW2 trial. [Abstract A2920: Thematic poster session B41: Monday, 21 May, 2012; 08:15–16:30].
• Korenblat P, et al. NVA237 once daily improves dyspnea and health-related quality of life in patients with COPD: The GLOW2 trial. [Abstract A2254: Poster discussion session A101: Sunday, 20 May, 2012; 14:00–16:30].
• Kerwin E, et al. NVA237 once daily reduces COPD exacerbations with similar rates to tiotropium: The GLOW2 trial. [Abstract A2255: Poster discussion session A101: Sunday, 20 May, 2012; 14:00–16:30].
Company: Novartis (Switzerland)
Product: NVA237 (glycopyrronium bromide)
Action
mechanism: Seebri® Breezhaler® (glycopyrronium bromide/NVA237) is an investigational long-acting muscarinic antagonist (LAMA) developed as a once-daily inhaled maintenance therapy for the treatment of COPD. Phase III data from the GLOW 1, 2 and 3 studies demonstrated that NVA237 increased patients\' lung function over a 24-hour period compared to placebo, with a fast onset of action at first dose, as well as improving exercise endurance.
Glycopyrronium bromide was licensed to Novartis in April 2005 by Vectura and its co-development partner Sosei. It was submitted for regulatory approval in Europe in Q3 2011 and Japan in Q4 2011, and expected US filing is the beginning of 2014.
Disease: chronic obstructive pulmonary disease
Therapeutic area: Respiratory diseases
Country:
Trial
details: GLOW2 was a 52-week double-blind, placebo-controlled, parallel-group study involving 1,066 patients to assess the efficacy, safety and tolerability of NVA237 in patients with COPD. Patients were randomized into three treatment arms receiving either once-daily NVA237 50 mcg or placebo (double-blind), or once-daily tiotropium 18 mcg (open label). They were also permitted to use COPD background therapy and rescue medication.
Latest
news: Novartis has announced that data from the pivotal Phase III GLOW2 study will be presented at the 2012 American Thoracic Society (ATS) International Conference May 18-23, 2012 in San Francisco, CA, USA. Results from this study demonstrated that once-daily (QD) 50 mcg NVA237 (glycopyrronium bromide) was superior to placebo in improving lung function, symptom relief and quality of life, and reducing exacerbations over a one-year period.
GLOW2 met its primary endpoint by demonstrating NVA237 provided superior 24-hour bronchodilation compared to placebo at 12 weeks measured by mean trough FEV1 (97 mL; p<0.001). At this same time point, trough FEV1 (Forced Expiratory Volume in the first second) for open-label (OL) tiotropium was 83 mL versus placebo (p<0.001). In addition, NVA237 showed similar efficacy to OL tiotropium (Spiriva® HandiHaler®*/18 mcg) in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). NVA237 also demonstrated rapid onset of action (within five minutes at first dose) and sustained 24-hour bronchodilation over 52 weeks.
At Day 1, Week 26 and Week 52 of the GLOW2 study, NVA237 showed significantly improved lung function (measured by mean trough FEV1) compared to placebo (all p<0.001) and results were similar to those seen with OL tiotropium[1]. At Day 1 and Week 12, 26 and 52, the FEV1 area under the curve (AUC) for 0-4 hr, 0-12 hr, 12-24 hr, and 0-24 hr for NVA237 was superior to placebo (p<0.05) and numerically greater than OL tiotropium.
The study also demonstrated that NVA237 improved COPD symptoms and quality of life and reduced exacerbations compared to placebo. NVA237 significantly reduced breathlessness (measured by the transition dyspnea index or TDI, p=0.002), improved health-related quality of life (measured by the St George\'s Respiratory Questionnaire or SGRQ, p<0.001), reduced use of rescue medication (p=0.039), and increased the percentage of days with no daytime symptoms (p<0.05)compared to placebo over 52 weeks.
For these symptomatic and quality of life indicators, results were numerically similar to those observed with OL tiotropium over the same time period[2]. NVA237 also significantly prolonged the time to first exacerbation and significantly reduced the rate of moderate/severe exacerbations versus placebo over 52 weeks (p=0.001); these effects were similar to OL tiotropium (p=0.001).
Throughout the GLOW2 study, NVA237 was well-tolerated with a similar incidence of adverse events to placebo and OL tiotropium[3]. Serious adverse events were reported less frequently with NVA237 (12.6%) than with either placebo (15.4%) or OL tiotropium (15.0%).
NVA237 has now been submitted for EU approval under proposed brand name Seebri® Breezhaler®. US filing is expected in 2014.
