European Commission and Japan approve once-daily dual bronchodilator Ultibro Breezhaler (QVA149) nearly simultaneously, for COPD patients

Novartis announced today that the European Commission approved once-daily Ultibro^® Breezhaler^® (indacaterol 85 mcg / glycopyrronium 43 mcg) as a maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD).  In addition, the Japanese Ministry of Health, Labour and Welfare (MHLW) approved once-daily Ultibro^® Inhalation Capsules (glycopyrronium 50 mcg / indacaterol 110 mcg), delivered through the Breezhaler^® device, for relief of various symptoms due to airway obstruction in chronic obstructive pulmonary disease (COPD). Ultibro^® Breezhaler^® / Ultibro^® Inhalation Capsules were developed under the name QVA149.

“We are very pleased that the European Commission and Japan approved QVA149, nearly simultaneously, for COPD patients. This rapid approval in Japan reflects our build-up of clinical trial and regulatory capabilities in Japan,” said David Epstein, Division Head, Novartis Pharmaceuticals. “Many COPD patients will now have a better treatment option, including first-line therapy with the launch of Ultibro Breezhaler in Europe.”

Dual bronchodilation with QVA149 is expected to set a new standard of care in COPD by combining the proven efficacy benefits and safety profiles of two established Novartis COPD treatments: the LABA*, Onbrez^® Breezhaler^® (indacaterol); and the LAMA**, Seebri^® Breezhaler^® (glycopyrronium bromide). Both these components are delivered through the Breezhaler^® device, as is QVA149, and are widely available around the world.

The approvals of QVA149 in Europe and Japan were based on the comprehensive IGNITE Phase III clinical trial program, one of the largest international trial programs in COPD comprising 11 studies in total with more than 10,000 patients from 52 ^{countries1-3,6-15}. From the eight IGNITE studies which completed in 2012^1-3,6-10, data showed that QVA149 significantly improved lung function versus several current standard ^{treatments1-3,6} and showed significant symptomatic improvements versus placebo in breathlessness, exercise tolerance, rescue medication use and health-related quality of ^life1,2,6. QVA149 also demonstrated statistically significant symptomatic improvements in breathlessness, rescue medication use and health-related quality of life compared to open-label (OL) tiotropium 18 ^mcg1. The rate of all COPD exacerbations (mild, moderate and severe) was significantly improved with QVA149 compared to glycopyrronium 50 mcg and OL tiotropium 18 ^mcg3.

“Since 2007, Novartis has received approvals for 15 new treatments and 16 new indications for existing treatments in Japan,” said Timothy Wright, Global Head Development, Novartis Pharmaceuticals. “Japan plays a critical role in our global clinical research program. In the last five years, Novartis has conducted 175 clinical studies in Japan with over 14,000 patients.”

In clinical studies, QVA149 demonstrated an acceptable safety profile with no meaningful differences between the treatment groups (placebo, indacaterol 150 mcg, glycopyrronium 50 mcg, OL tiotropium 18 mcg, salmeterol / fluticasone (SFC) 50 mcg / 500 mcg) in the incidence of adverse and serious adverse ^events1-3,6. The safety profile was characterized by typical anticholinergic and beta-adrenergic effects related to the individual components of the ^{combination1-3,6-10}.

COPD is a progressive disease affecting up to 10% of adults across ^Europe4 and is projected to be the third leading cause of death by 2020.⁵ In addition, 5.3 million patients are currently living with COPD in Japan.

About the Novartis respiratory portfolio

Novartis is committed to addressing the unmet medical needs of COPD patients and improving their quality of life by providing innovative medicines and devices.

^Seebri® Breezhaler^® / Seebri^® Inhalation Capsules (glycopyrronium bromide) are a once-daily inhaled long-acting muscarinic antagonist (LAMA; also referred to as a long-acting anticholinergic) indicated as a maintenance bronchodilator treatment to relieve symptoms in adult patients with ^COPD15. Glycopyrronium bromide was exclusively licensed to Novartis in April 2005 by Vectura and its co-development partner Sosei. In Phase III studies (GLOW 1, 2 and 3), once-daily glycopyrronium 50 mcg demonstrated rapid improvements in lung function after first dose on Day 1 which was sustained for 24 hours and maintained over the 52 week study period compared with ^placebo16-18. Glycopyrronium 50 mcg also significantly improved shortness of breath, health-related quality of life, exacerbation risk, and exercise endurance versus ^placebo16-18. Glycopyrronium is approved in the EU, Japan, Switzerland, Canada a number of other countries.

^Onbrez® Breezhaler^® / Onbrez^® Inhalation Capsules (indacaterol) are a once-daily inhaled long-acting _beta2-adrenergic agonist (LABA) that offer clinically relevant 24 hour bronchodilation combined with a rapid onset of action within five minutes at first dose, as demonstrated in the INERGIZE Phase III trial ^program19-33. Indacaterol 150 mcg provided greater clinical benefit in terms of reduced shortness of breath, lower use of rescue medication and improved health status, compared with blinded tiotropium bromide 18 ^mcg30. Indacaterol was first approved and launched in the EU (150 mcg and 300 mcg once-daily doses) for maintenance bronchodilator treatment of airflow obstruction in adult patients with ^COPD34. It has now received approvals in more than 100 countries around the world including Japan (as Onbrez^® Inhalation Capsules 150 mcg once-daily) and USA (as ^{ArcaptaTM NeohalerTM} 75 mcg once-daily).

^Ultibro® Breezhaler^® / Ultibro^® Inhalation Capsules (QVA149) are an inhaled, once-daily, fixed-dose combination of glycopyrronium bromide and indacaterol maleate. QVA149 was investigated for the treatment of COPD in the Phase III IGNITE clinical trial program. IGNITE is one of the largest international clinical trial programs in COPD comprising 11 studies in total (ILLUMINATE, SHINE, BRIGHT, ENLIGHTEN, SPARK, BLAZE, ARISE, BEACON, RADIATE, LANTERN, FLAME) with more than 10,000* patients across 52 ^{countries1-3,5-14}. The first eight studies (ILLUMINATE, SHINE, BRIGHT, ENLIGHTEN, SPARK, BLAZE, ARISE, BEACON) completed in 2012^1-3,5-9. The studies were designed to investigate efficacy (lung function, exercise endurance, exacerbations, shortness of breath and quality of life), safety and tolerability of patients treated with ^{QVA1491-3,5-12}.

*Total refers to all 11 IGNITE studies.

Results from the Phase III IGNITE trials have demonstrated statistically significant improvements in bronchodilation with QVA149 versus several ^{treatments1-3,5} widely used as current standards of care. Data showed that QVA149 significantly improved lung function compared to OL tiotropium 18 mcg, fixed dose combination SFC 50 mcg / 500 mcg, indacaterol maleate 150 mcg, glycopyrronium 50 mcg and placebo providing a rapid onset of action within five minutes, and sustained bronchodilation during a 24 hour period which was maintained for up to 26 ^weeks2,5. In the IGNITE phase III trial program, QVA149 also showed symptomatic improvements versus placebo in COPD ^{patients1,2,5}. These symptomatic improvements included breathlessness, exercise tolerance, rescue medication use and health-related quality of ^life1,2,5. QVA149 also significantly improved the rate of all COPD exacerbations (mild, moderate and severe) compared to glycopyrronium 50 mcg and OL tiotropium 18 ^mcg3.

Novartis continues development of respiratory products for delivery via the Breezhaler^® device. This is a single-dose dry powder inhaler (SDDPI), which has low air flow resistance, making it suitable for patients with different severity of airflow ^limitation36. The Breezhaler^® device allows patients to hear, feel and see that they have taken the full dose ^correctly32.

About COPD

COPD is a progressive life-threatening disease that makes it hard to breathe, with symptoms that have a destructive impact on patients’ function and quality of ^life37. It affects an estimated 210 million people ^worldwide5 and is projected to be the third leading cause of death by 2020³⁷. COPD is often considered to be a disease of later years, but estimates suggest that 50% of those with COPD are now less than 65 years old, resulting in increases in absenteeism, premature ^retirement38 and reductions in workforce ^{participation38,39}.

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