Novartis’ new analyses reinforce the potential of Ultibro® Breezhaler®

Further analyses of Novartis’ head-to-head FLAME study suggest that inhaled corticosteroids (ICS) may not be needed in some chronic obstructive pulmonary disease (COPD) patients with high blood eosinophil (a type of white blood cell) counts. The new data showed that Ultibro® Breezhaler® consistently provided superior or similar benefits over Seretide®* in COPD patients regardless of the eosinophil count[1]. These results contrast with data suggesting better clinical outcomes with ICS therapies for patients with high eosinophil counts[2]-[5]. The data was published in the centenary issue of the American Thoracic Society’s ‘Blue Journal’**[1] and solidifies the need for individualized risk-benefit assessments when considering ICS treatments.

The potential for high blood eosinophil counts to be considered as a biomarker to direct the use of a LABA***/ICS combination over dual bronchodilation (LABA/LAMA****) in some patients, has been referenced in the 2017 GOLD (Global Initiative for Chronic Obstructive Lung Disease) report[6]. FLAME was the first trial to prospectively study the influence of blood eosinophils on the efficacy of ICS-containing therapies versus a LABA/LAMA. The new analyses showed that once-daily Ultibro Breezhaler (indacaterol/glycopyrronium) 110/50 mcg was superior to twice-daily Seretide (salmeterol/fluticasone [SFC]) 50/500 mcg in reducing exacerbations (flare-ups), independent of a blood eosinophil count above or below 2%[1]. In addition, at no cut-off was Seretide more effective than Ultibro Breezhaler[1].

“These new FLAME study analyses provide evidence that an effective dual bronchodilator such as Ultibro Breezhaler can provide similar or better benefits in patients with high eosinophil counts who may have been considered for an inhaled steroid-containing treatment,” said Vasant Narasimhan, Global Head Drug Development and Chief Medical Officer for Novartis. “The data highlight the opportunity to allow more patients to avoid unnecessary exposure steroid-containing regimens and the significant potential associated risks.”

With funding support from Novartis, the International Primary Care Respiratory Group (IPCRG) is addressing the appropriate use and safe withdrawal of ICS in COPD patients with the launch of a primary care physician guide. The guide was launched at the recent IPCRG conference in Slovenia and aims to ensure the latest evidence based treatment guidance from the 2017 GOLD report is translated into daily clinical practice. The guide is accessible on the IPCRG website here: https://goo.gl/FlSVck (link is external)

FLAME is 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[7].

Results published in the New England Journal of Medicine[7] confirmed that Ultibro Breezhaler (indacaterol/glycopyrronium) 110/50 mcg met its primary endpoint (non-inferiority) and furthermore demonstrated superiority to Seretide (salmeterol/fluticasone [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[7]:

The pre-specified analyses of data from the FLAME study compared treatment efficacy according to blood eosinophil percentage (<2% and >=2%, <3% and >=3%, and <5% and >=5%) and absolute blood eosinophil count (<=150 cells/ Mu l, 150 to <300 cells/ Mu l, and >=300cells/ Mu l)[1].

FLAME is part of the IGNITE Phase III clinical trial program exploring Ultibro Breezhaler for the treatment of COPD

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® (indacaterol), which are all indicated as maintenance treatments for COPD patients. Glycopyrronium bromide and certain use and formulation intellectual property were exclusively licensed to Novartis in April 2005 by Sosei and Vectura.

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[8]. The Breezhaler device allows patients to hear, feel and see that they have taken the full dose correctly[8],[9].

Chronic obstructive pulmonary disease (COPD) affects an estimated 210 million people worldwide[10] and is the third leading cause of death[11]. It is progressive (usually gets worse over time) and can be a life-threatening disease[10],[12]. COPD makes it difficult to breathe, with symptoms that have a destructive impact on patients’ function (i.e. activity limitation, decreased mobility) and quality of life[10],[12].

Exacerbations are a sudden worsening of COPD symptoms that can be frightening for patients, causing distress, anxiety and quality of life deterioration[13]. COPD exacerbations are also associated with significant healthcare resource burden and costs[14], particularly due to the frequent need for hospitalization. Consequently, the prevention of exacerbations is an important goal in COPD management to improve long-term health status and conserve healthcare resources[15].