Novartis AG Announces Robust Phase 3 Results For QVA149 And NVA237 And Submits Regulatory Applications To U.S. FDA

Phase III results for QVA149 and NVA237 met their primary endpoints and significantly improved lung function in COPD patients[1-5]

Basel, January 8, 2015 - Novartis announced today positive top-line results from the pivotal Phase III clinical trial programs for QVA149 (indacaterol/glycopyrronium bromide) and NVA237 (glycopyrronium bromide) to support New Drug Applications (NDAs) with the US Food and Drug Administration (FDA) for the long-term maintenance treatment of chronic obstructive pulmonary disease (COPD). The results from the EXPEDITION (including FLIGHT 1, 2 and 3 studies) and GEM clinical trial programs met their primary and secondary endpoints.

COPD symptoms can negatively impact a patient’s ability to breathe and perform essential daily activities, thereby reducing their quality of life[6,7]. There is an urgent need for new treatment options in COPD because many patients remain symptomatic despite medical therapy[8].

“These data once again confirm the strong efficacy and favourable safety profiles of both QVA149 and NVA237,” said Vasant Narasimhan, Global Head of Development, Novartis Pharmaceuticals. “With submissions to the US FDA now complete for both treatments, we are closer to offering US patients with COPD a broader range of treatment options to help improve the significant burden of reduced lung function, and to help improve their lives.”

The FLIGHT 1 and 2 studies met their primary objectives with twice-daily QVA149 demonstrating statistically significant and clinically meaningful improvements in lung function (FEV₁ AUC_0-12) at Week 12, compared to indacaterol and glycopyrronium bromide in moderate-to-severe COPD patients[1,2,9]. Improvements in overall health status, a secondary endpoint based on the St George’s Respiratory Questionnaire (SGRQ) total score, and rescue medication usage were also seen with QVA149 compared to placebo at Week 12[1,2]. The common adverse events reported for QVA149 were comparable to the individual components and placebo across the EXPEDITION studies[1,2].

In the GEM 1 and 2 studies, twice-daily NVA237 demonstrated significant and clinically meaningful improvements in lung function (FEV₁ AUC_0-12h) at Week 12 in moderate-to-severe COPD patients compared to placebo; meeting its primary objective[4,5,9]. An improvement in health status was also observed in patients at Week 12. The adverse events reported for NVA237 were comparable to placebo across the GEM studies[4,5]. Data from the EXPEDITION and GEM programs are expected to be presented at major medical congresses later this year.

About EXPEDITION
The EXPEDITION Program consisted of studies, including FLIGHT 1 and 2, which were identical 12-week, multi-center, randomized, double blind, parallel-group, placebo and active controlled studies to assess the efficacy, safety, and tolerability of QVA149 (indacaterol/glycopyrronium bromide) in moderate-to-severe COPD patients. The primary objective was to compare twice-daily QVA149 27.5/12.5 mcg to its monotherapy components in terms of lung function (FEV₁ AUC_0-12h) at Week 12[1,2].

FLIGHT 3 was a 52-week randomized double blind, parallel-group study to assess the safety and tolerability of twice-daily QVA149 27.5/12.5 mcg compared to once-daily indacaterol 75 mcg in moderate-to-severe COPD patients. The primary endpoint was the overall rate of adverse events reported during the study[3].

About GEM
GEM 1 and 2 were 12-week multi-center, randomized, double-blind, placebo controlled studies to assess the efficacy and safety of twice-daily NVA237 (glycopyrronium bromide) 12.5 mcg in moderate-to-severe COPD patients. The primary objective was to compare twice-daily NVA237 to placebo in terms of lung function (FEV₁ AUC_0-12h) after 12 weeks of treatment[4,5]. The objective of GEM 3 was to determine safety and tolerability of twice-daily NVA237 12.5 mcg compared to once-daily indacaterol 75 mcg in moderate-to-severe COPD patients.

About QVA149
Twice-daily QVA149 (indacaterol/glycopyrronium bromide) 27.5/12.5 mcg, as used in the EXPEDITION program, is being submitted for US registration only. Outside of the US, QVA149 has been developed/marketed as Ultibro Breezhaler 110/50 mcg, which is a once-daily maintenance bronchodilator treatment to relieve symptoms in adult patients with COPD[10]. Once-daily Ultibro® Breezhaler® is currently approved for use in over 50 countries, including countries within the EU and Latin America, Japan, Canada, Switzerland and Australia.

About NVA237
Twice-daily NVA237 (glycopyrronium bromide) 12.5 mcg, as used in the GEM trials, is being submitted for US registration only. Outside of the US, NVA237 has been developed/marketed as Seebri^® Breezhaler^® 50 mcg, which is a once-daily medication indicated as a maintenance bronchodilator treatment to relieve symptoms in adult patients with COPD and is approved for use in over 70 countries, including countries within the EU and Latin America, Japan, Canada, Switzerland and Australia[11].

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 QVA149/Ultibro Breezhaler (indacaterol/glycopyrronium bromide), NVA237/Seebri Breezhaler (glycopyrronium bromide) and Onbrez® Breezhaler®/Arcapta®Neohaler(TM) (indacaterol inhalation powder), 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.

Worldwide, 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[12]. The Breezhaler device allows patients to hear, feel and see that they have taken the full dose correctly[10,12].

About COPD
COPD is associated with chronic morbidity and mortality and The World Health Organization (WHO) estimates that 210 million people worldwide have COPD[13]. Deaths from COPD are projected to increase over the next 10 years by more than 30% unless underlying risk factors are addressed[14]. COPD is the third leading cause of death in America, claiming the lives of 134,676 Americans in 2010[15] and COPD is now the third leading cause of death worldwide[16].

COPD is progressive (usually gets worse over time), and can be a life-threatening disease[7,13]. It 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[7,15]. It 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[17,18].

Disclaimer
The foregoing release contains forward-looking statements that can be identified by words such as “support,” “can,” “offering,” “committed,” “continues,” “projected,” “suggest,” or similar terms, or by express or implied discussions regarding potential marketing approvals for QVA149 and NVA237, or regarding potential future revenues from any or all of the products in the Novartis COPD portfolio, including QVA149 and NVA237. 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 QVA149 or NVA237 will be submitted in any additional markets, or approved for sale in any market where they have been submitted, 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 and over-the-counter 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 130,000 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] Clinicaltrials.gov. A 12 Week Treatment, Multi-center, Randomized, Double-blind, Parallel-group, Placebo and Active Controlled Study to Assess the Efficacy, Safety, and Tolerability of Indacaterol Maleate / Glycopyrronium Bromide in COPD Patients With Moderate to Severe Airflow Limitation. (FLIGHT 1). CQVA149A2336. http://clinicaltrials.gov/ct2/show/NCT01727141?term=CQVA149A2336&rank=1 [Accessed 17 November 2014].
[2] Clinicaltrials.gov. A 12-week Treatment, Multi-center, Randomized, Double-blind, Parallel-group, Placebo and Active Controlled Study to Assess the Efficacy, Safety, and Tolerability of Indacaterol Maleate / Glycopyrronium Bromide in COPD Patients With Moderate to Severe Airflow Limitation. (FLIGHT 2). CQVA149A2337. http://clinicaltrials.gov/ct2/show/NCT01712516?term=CQVA149A2337&rank=1 [Accessed 17 November 2014].
[3] Clinicaltrials.gov. A Multi-centre Randomized Double Blind 52-week Study to Assess the Safety of QVA149 Compared to QAB in Patients With COPD Who Have Moderate to Severe Airflow Limitation. (FLIGHT 3). QVA149A2340. http://clinicaltrials.gov/ct2/show/NCT01682863?term=QVA149A2340&rank=1 [Accessed 17 November 2014].
[4] Clinicaltrials.gov. NVA237 BID Versus Placebo Twelve-week Efficacy Study. (GEM 1). NVA237A2317. http://clinicaltrials.gov/ct2/show/NCT01709864?term=NVA237A2317&rank=1 [Accessed 17 November 2014].
[5] Clinicaltrials.gov. NVA237 BID Versus Placebo Twelve-week Efficacy Study. (GEM 2). NVA237A2318. http://clinicaltrials.gov/ct2/show/NCT01715298?term=NVA237A2318&rank=1 [Accessed 17 November 2014].
[6] World Health Organization: Chronic Obstructive Pulmonary Disease (COPD) Fact Sheet. http://www.who.int/mediacentre/factsheets/fs315/en/. [Accessed 09 December 2014].
[7] Joshi M, Joshi A, Bartter T. Symptom burden in chronic obstructive pulmonary disease and cancer. Curr Opin Pulm Med 2012;18:97-103.
[8] Price D, West D, Brusselle G, et al. Management of COPD in the UK Primary-Care Setting: An Analysis of Real-Life Prescribing Patterns. International Journal of COPD. 2014;9:889-905.
[9] Donohue JF. Minimal clinically important differences in COPD lung function. COPD. 2005 Mar;2(1):111-24.
[10] Ultibro Breezhaler EU Summary of Product Characteristics. [Online] 3 October 2013. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002679/WC500151255.pdf [Accessed 23 July 2014].
[11] EMA (2012). Seebri Breezhaler EU Summary of product characteristics. [Online] Revised 28 September 2012 http://www.medicines.org.uk/emc/medicine/27138/SPC/Seebri+Breezhaler+Inhalation+Powder,+Hard+Capsules+44mcg/ [Accessed 1 August 2014].
[12] Pavkov 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.
[13] Global Alliance Against Chronic Respiratory Diseases (GARD). 8^th General Meeting. Available at: http://www.who.int/gard/publications/GARDGMreport2013.pdf. [Accessed on 17 November 2014].
[14] World Health Organization: Chronic Obstructive Pulmonary Disease (COPD) Fact Sheet. http://www.who.int/respiratory/copd/en/ [Accessed 12 December 2014]
[15] National Vital Statistics Report (NVSR): Deaths: Final Data for 2012. http://www.cdc.gov/nchs/data/nvsr/nvsr63/nvsr63_09.pdf. [Accessed 09 December 2014].
[16] World Health Organization: Chronic Obstructive Pulmonary Disease (COPD) Fact Sheet. http://www.who.int/mediacentre/factsheets/fs310/en/ . [Accessed 09 December 2014].
[17] DaCosta M et al. The burden of chronic obstructive pulmonary disease among employed adults. Int J Chron Obstruct Pulmon Dis 2012;7:211-219. Published online 2012 March 19. doi: 10.2147/COPD.S29280. [Accessed 17 November 2014].
[18] 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.

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