Novartis’ INSTEAD study for Onbrez® Breezhaler® in patients with moderate COPD meets primary objective

Novartis’ INSTEAD study for Onbrez® Breezhaler® in patients with moderate COPD meets primary objective

Results confirm non-inferiority of Onbrez® Breezhaler® (indacaterol) in lung function compared to Seretide®  * (salmeterol/fluticasone) in the studied population

In INSTEAD study, patients with moderate COPD and no exacerbations in the past year were switched from salmeterol/fluticasone to Onbrez Breezhaler

Study showed similar symptomatic benefits in terms of shortness of breath and health status in patients treated with Onbrez Breezhaler compared to those on salmeterol/fluticasone

Basel, April 25, 2014  Novartis announced today top-line results from the Phase IV INSTEAD switch study in patients with chronic obstructive pulmonary disease (COPD),  which met its primary objective. Once-daily Onbrez® Breezhaler® (indacaterol) 150 mcg demonstrated non-inferiority in lung function at week 12 to twice-daily Seretide®* (salmeterol/fluticasone propionate (SFC)) 50/500 mcg in patients with moderate COPD  and no exacerbations in the previous year. 

The INSTEAD switch study also showed similar symptomatic benefits in terms of  shortness of breath and health status after 12 and 26 weeks in patients treated with  Onbrez Breezhaler compared to those on SFC. The safety profile of Onbrez Breezhaler observed in this study was consistent with previously reported results from Phase III studies. 

“These positive results help inform the switch from salmeterol/fluticasone to Onbrez Breezhaler in patients with moderate COPD and who are at low risk of exacerbations.   This confirms that Onbrez Breezhaler provides an effective maintenance treatment option for these patients,” said Tim Wright, Global Head of Development, Novartis Pharmaceuticals. “In addition, these results support international guidelines, which advise against the use of inhaled corticosteroids due to long-term risks in COPD patients  at low risk of exacerbations ¹“.

COPD affects an estimated 210 million people worldwide² and is projected to be the third leading cause of death by 2020¹. Treatments that effectively control the symptoms of COPD and allow patients to continue with their daily activities are very important in helping address the unmet needs in the management of COPD^3,4.

INSTEAD was a global, randomized, double-blind, parallel-group, 26-week study. This study randomized 581 patients with moderate COPD who had been taking SFC* for at least three months to either continue on SFC* or switch to indacaterol. The primary objective of this study was to demonstrate the non-inferiority of indacaterol versus SFC* in lung function (trough FEV¹) after 12 weeks of treatment in patients with moderate COPD who had experienced no exacerbations in the previous year. Data from this study are expected to be presented at major medical congresses later this year.

About Onbrez Breezhaler 
Onbrez Breezhaler (indacaterol) is a once-daily inhaled long-acting beta2-adrenergic agonist (LABA) that offers 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 program5,18. Onbrez Breezhaler 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 18 mcg16. Onbrez Breezhaler 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 COPD19. It has now received approvals in more than 100 countries around the world and is available in Japan (as Onbrez Inhalation Capsules 150 mcg once-daily) and in the USA (as ArcaptaTM NeohalerTM 75 mcg once-daily).

About the Novartis COPD 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. The Novartis 
COPD portfolio includes Onbrez® Breezhaler®/ Arcapta® Neohaler® (indacaterol), Seebri® Breezhaler® (glycopyrronium bromide) and Ultibro® Breezhaler® (indacaterol /glycopyrronium bromide), 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 limitation²⁰. The Breezhaler device allows patients to hear, feel and see that they have taken the full dose correctly^19,20.

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^1,21. 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 and reductions in workforce participation^3,4.

*In some countries, Seretide^® (salmeterol/fluticasone) 50/500 mcg is indicated for the symptomatic treatment of patients with COPD, with a FEV <60% predicted normal (prebronchodilator) and a history of repeated exacerbations, who have significant symptoms despite regular bronchodilator therapy. The patient population in the INSTEAD study who received salmeterol/fluticasone were moderate COPD patients who had not exacerbated twelve months prior to entry. The INSTEAD study used the Accuhaler^® dry powder inhaler, also known as Diskus^®. Seretide^®, Diskus^® and Accuhaler^® are registered trademarks of the GlaxoSmithKline group of companies.

Disclaimer 
The foregoing release contains forward-looking statements that can be identified by words such as “projected,” “expected,” “later this year,” “committed,” “continues,” Or similar terms, or by express or implied discussions regarding potential new indications or labeling for Onbrez Breezhaler, or regarding potential future revenues from any or all of the products in the Novartis COPD portfolio, including Onbrez Breezhaler. You should not place undue reliance on these statements. Such forward-looking statements are based on the current beliefs and expectations of management regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or 
more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that Onbrez Breezhaler will be submitted or approved for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that any of the products in the Novartis COPD portfolio will receive additional regulatory approvals or be commercially successful in the future. In particular, management’s expectations regarding these products could be affected by, among other things, the uncertainties inherent in research and development, including unexpected clinical trial results and additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; the company’s ability to obtain or maintain proprietary intellectual property protection; general economic and industry conditions; global trends toward health care cost containment, including ongoing pricing pressures; unexpected manufacturing issues, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. 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, over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 2013, the Group achieved net sales of USD 57.9 billion, while R&D throughout the Group amounted to approximately USD 9.9 billion (USD 9.6 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 135,000 full-time-equivalent 
associates and sell products in more than 150 countries around the world. For more information, please visit http://www.novartis.com.

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References

1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and 
Prevention of Chronic Obstructive Pulmonary Disease. Updated 2014. http://www.goldcopd.org/uploads/users/files/GOLD_Report2014_Feb07.pdf . [Accessed 14 April 2014].

2. Global Alliance Against Chronic Respiratory Diseases (GARD). Global surveillance, prevention and control of chronic respiratory diseases: a comprehensive approach.  Available at: http://www.who.int/gard/publications/GARD_Manual/en/. [Accessed 14 April 2014].

3. Fletcher MJ et al. COPD Uncovered: An International survey on the impact of chronic obstructive pulmonary disease (COPD) on a working age population. BMC Public Health 2011;11:612.

4. daCosta M et al. The burden of chronic obstructive pulmonary disease among employed adults. Int J Chron ObstructPulmon Dis 2012;7:211-219. Published online 2012 March 19. doi: 10.2147/COPD.S29280. [Accessed 14 April 2014].

5. Vogelmeier C et al. Indacaterol provides 24-hour bronchodilation in COPD: a placebo-controlled blinded comparison  with tiotropium. Respir Res 2010;11:135.

6. Balint B et al. Onset of action of indacaterol in patients with COPD: comparison with salbutamol and salmeterol-fluticasone. Int J Chron Obstruct Pulmon Dis 2010;5:311-318.

7. La Force C et al. Sustained 24-hour efficacy of once-daily indacaterol (300 g) in patients with chronic obstructive pulmonary disease: a randomized, crossover study. Pulm Pharmacol Ther 2011;24:162-168.

8. Beeh KM, Wagner F, Khindri S, Drollmann AF. Effect of indacaterol on dynamic lung hyperinflation and breathlessness in hyperinflated patients with COPD. COPD 2011;8(5):340 345.

9.O’ Donnell DE et al. Effect of indacaterol on exercise endurance and lung hyperinflation in COPD. Respir Med 2011; 105(7):1030-1036.

10. Magnussen H et al. Indacaterol once-daily is equally effective dosed in the evening or morning in COPD. Respir Med2010;104:1869-1876.

11. Feldman G et al. Efficacy and safety of indacaterol 150 µg once-daily in COPD: a double-blind, randomised, 12-week study. BMC Pulm Med 2010;10:11.

12. Barnes PJ et al. Integrating indacaterol dose selection in a clinical study in COPD using an adaptive seamless design. Pulm Pharmacol Ther 2010;23:165 171.

13. Donohue JF et al. Once-daily bronchodilators for chronic obstructive pulmonary disease: indacaterol versus tiotropium. Am J Respir Crit Care Med 2010;182:155-162.

14. Kornmann O et al. Once-daily indacaterol vs twice-daily salmeterol for COPD: a placebo-controlled comparison. EurRespir J 2011;37:273-279.

15. Dahl R et al. Efficacy of a new once-daily long-acting inhaled beta2-agonist, indacaterol, versus twice-daily formoterol in COPD. Thorax 2010;65:473-479.

16. Buhl R et al. Blinded 12-week comparison of once-daily indacaterol and tiotropium in COPD. Eur Respir J 2011; 38:797-803.

17. Chapman KR et al. Long-term safety and efficacy of indacaterol, a novel long-acting²-agonist, in subjects with COPD: a randomized, placebo-controlled study. Chest 2011;140;68-75.

18. Korn S et al. Indacaterol once-daily provides superior efficacy to salmeterol twice-daily in COPD: a 12-week study. Respir Med 2011;105:719-726.

19. EMA, 2012. Onbrez^® Breezhaler^® (indacaterol) EU Summary of Product Characteristics. [Online] July 26, 2012  Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_- _Product_Information/human/001114/WC500053732.pdf. [Accessed 14 April 2014].

20. Pavkov R et al. Characteristics of a capsule based dry powder inhaler for the delivery of indacaterol. CMRO 2010; 26; 11:2527 2533. doi:10.1185/03007995.2010.518916.

21. Joshi M et al. Symptom burden in chronic obstructive pulmonary disease and cancer. Obstructive, occupational and environmental diseases. 2012;18(2).

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