Novartis first-in-class once-daily dual bronchodilator Ultibro Breezhaler (QVA149) achieves near simultaneous approval for COPD patients in Europe and Japan

• Ultibro® Breezhaler® (QVA149) is the first once-daily dual bronchodilator to gain European Commission approval as a maintenance bronchodilator treatment to relieve symptoms in adult patients with COPD
• In Japan, once-daily Ultibro® Inhalation Capsules (QVA149), delivered through the Breezhaler® device, approved for relief of various symptoms due to airway obstruction in COPD
• Pivotal Phase III IGNITE data showed QVA149 significantly improved lung function and patient-reported outcomes including breathlessness and rescue medication use, compared to current standards of care[1]-[3].
• Since 2007, Novartis has received approvals for 15 new treatments and 16 new indications for existing treatments in Japan underlining our commitment to clinical research in Japan, with investments of 51 billion Japanese Yen

BASEL, Switzerland I September 23, 2013 I 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 countries[1]-[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 treatments[1]-[3],[6] and showed significant symptomatic improvements versus placebo in breathlessness, exercise tolerance, rescue medication use and health-related quality of life[1],[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 mcg[1]. The rate of all COPD exacerbations (mild, moderate and severe) was significantly improved with QVA149 compared to glycopyrronium 50 mcg and OL tiotropium 18 mcg[3].

 “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 events[1]-[3],[6]. The safety profile was characterized by typical anticholinergic and beta-adrenergic effects related to the individual components of the combination[1]-[3],[6]-[10].

 COPD is a progressive disease affecting up to 10% of adults across Europe[4] 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 COPD[15]. 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 placebo[16]-[18]. Glycopyrronium 50 mcg also significantly improved shortness of breath, health-related quality of life, exacerbation risk, and exercise endurance versus placebo[16]-[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 program[19]-[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 mcg[30]. Indacaterolwas 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 COPD[34]. 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 Arcapta^TM Neohaler^TM 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 countries[1]-[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 QVA149[1]-[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 treatments[1]-[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 weeks[2],[5]. In the IGNITE phase III trial program, QVA149 also showed symptomatic improvements versus placebo in COPD patients[1],[2],[5]. These symptomatic improvements included breathlessness, exercise tolerance, rescue medication use and health-related quality of life[1],[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 mcg[3].

 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 limitation[36]. The Breezhaler^® device allows patients to hear, feel and see that they have taken the full dose correctly[32].

 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 life[37]. It affects an estimated 210 million people worldwide[5] and is projected to be the third leading cause of death by 2020[37]. 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 retirement[38] and reductions in workforce participation[38],[39].

 Disclaimer

The foregoing release contains forward-looking statements that can be identified by terminology such as “commitment,” “will,” “expected,” “projected,” “committed,” “continues,” or similar expressions, or by express or implied discussions regarding potential additional regulatory approvals for Ultibro or regarding potential future revenues from Ultibro or other Novartis respiratory products. You should not place undue reliance on these statements.  Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Ultibro will be approved for sale in any market or at any particular time. Nor can there be any guarantee that Ultibro or other Novartis respiratory products will achieve any particular levels of revenue in the future. In particular, management’s expectations could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; competition in general; government, industry and general public pricing pressures; the company’s ability to obtain or maintain patent or other proprietary intellectual property protection; unexpected manufacturing issues; the impact that the foregoing factors could have on the values attributed to the Novartis Group’s assets and liabilities as recorded in the Group’s consolidated balance sheet, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

 About Novartis

Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, preventive vaccines and diagnostic tools, over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 2012, the Group achieved net sales of USD 56.7 billion, while R&D throughout the Group amounted to approximately USD 9.3 billion (USD 9.1 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 131,000 full-time-equivalent associates and operate in more than 140 countries around the world. For more information, please visit  http://www.novartis.com.

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SOURCE: Novartis