Novartis announced the New England Journal of Medicine publication of the head-to-head FLAME study comparing the efficacy of once-daily Ultibro Breezhaler (indacaterol/glycopyrronium bromide) 110/50 mcg to twice-daily Seretide (salmeterol/fluticasone [SFC]) 50/500 mcg in reducing chronic obstructive pulmonary disease (COPD) exacerbations. In addition to meeting the primary endpoint (non-inferiority), findings demonstrated the superiority of Ultibro Breezhaler over the widely used inhaled corticosteroid (ICS)/LABA combination on exacerbation outcomes. The published FLAME results are anticipated to impact the future management and treatment of COPD patients.

Preventing exacerbations is one of the primary goals of long-term care for COPD patients. These episodes have a detrimental effect on quality of life and disease progression, contributing to further lung function decline and, in severe cases, hospitalization and even death.

"Reducing exacerbations is absolutely critical to improve outcomes and quality of life for COPD patients," said Vasant Narasimhan, global head drug development and chief medical officer for Novartis. "The FLAME study has clearly shown that Ultibro Breezhaler is superior to the current standard of care in reducing exacerbations, marking a shift away from therapies containing steroids for the optimal treatment of COPD patients."

The results of FLAME confirmed that Ultibro Breezhaler is superior to SFC in reducing exacerbation outcomes regardless of a patient's disease severity and eosinophil levels (a type of white blood cell). Significantly, compared to SFC, Ultibro Breezhaler both reduced the rate of moderate or severe exacerbations with a 17% risk reduction (rate ratio, 0.83), and prolonged the time to the first of these episodes with a 22% risk reduction (hazard ratio, 0.78). The safety profiles of the two treatments were consistent with their known profiles. The incidence of pneumonia was higher with SFC than Ultibro Breezhaler (3.2% vs 4.8%: a statistically significant difference).

These data were also presented to the scientific community for the first time today at the 2016 Annual Meeting of American Thoracic Society (ATS) in San Francisco, USA.

FLAME was a randomized, double-blind, double-dummy, parallel-group, non-inferiority, active-controlled 52-week study involving 3,362 COPD patients and conducted at 356 sites across 43 countries.

Results confirmed that Ultibro Breezhaler 110/50 mcg met its primary endpoint (non-inferiority) and furthermore demonstrated superiority to SFC 50/500 mcg on the rate of all COPD exacerbations (mild/moderate/severe) over one year of treatment in COPD patients with a history of at least one exacerbation in the previous year.

Against further secondary endpoints, Ultibro Breezhaler was also superior compared to SFC in reducing or improving the following: Rate and time to first moderate or severe COPD exacerbation; Time to first COPD exacerbation (mild/moderate/severe); Time to first severe COPD exacerbation;  Lung function (trough FEV);  Health-related quality of life (St. George's Respiratory Questionnaire).

FLAME is part of the IGNITE phase III clinical trial programme exploring Ultibro Breezhaler for the treatment of COPD.

Ultibro Breezhaler 110/50 mcg is a once-daily LABA+/LAMA++ dual bronchodilator approved in the European Union (EU) as a maintenance bronchodilator treatment to relieve symptoms in adult patients with COPD. Clinical trials have shown that it offers statistically significant improvements in bronchodilation compared to treatments widely used as current standards of care, including SFC 50/500 mcg and open-label tiotropium (18 mcg). Ultibro Breezhaler is currently approved for use in over 80 countries worldwide, including countries within the EU and Latin America, Japan, Canada, Switzerland and Australia.  

Novartis is committed to addressing the unmet medical needs of COPD patients and improving their quality of life by providing innovative medicines and devices. The Novartis COPD portfolio includes Ultibro Breezhaler (indacaterol/glycopyrronium bromide), Seebri Breezhaler (glycopyrronium bromide) and Onbrez Breezhaler/Arcapta Neohaler (indacaterol), which are all indicated as maintenance treatments for COPD patients. Glycopyrronium bromide was exclusively licensed to Novartis in April 2005 by Vectura and its co-development partner Sosei.

Novartis continues development of respiratory products for delivery via the low resistance Breezhaler inhalation device, which makes it suitable for patients with different severities of airflow limitation. The Breezhaler device allows patients to hear, feel and see that they have taken the full dose correctly.