Health Canada grants priority review for Novartis' heart failure medicine LCZ696

• Decision could speed access to LCZ696 for Canadian patients with heart failure (NYHA class II-IV)  with systolic dysfunction (reduced ejection fraction)
• New Drug Submission will be based on results from the landmark PARADIGM-HF study¹
• Heart failure affects more than 500,000 Canadians² and is responsible for 9 per cent of all deaths in Canada³, a prevalence almost equal to death from breast, colorectal, prostate and pancreatic cancer combined⁴

DORVAL, QC, March 12, 2015 /CNW/ - Novartis Pharmaceuticals Canada Inc. announced today that Health Canada has granted priority review for the New Drug Submission (NDS) by Novartis for LCZ696, an investigational medicine for the treatment of heart failure (NYHA class II-IV) with systolic dysfunction (reduced ejection fraction) (HFrEF).

Priority review is granted by Health Canada following a preliminary review of clinical data when a new treatment appears to have the potential to offer significant clinical benefit, defined as "outcomes that have an overall positive impact on the treatment" of diseases that are "serious, life-threatening or severely debilitating"⁵.

Heart failure is one of the leading causes of death in Canada⁶ and the second leading cause of hospitalization of Canadians age 65 or older⁷. Priority review by Health Canada means the review could be completed in about seven months from the date of submission⁸.

"We are very pleased that Health Canada has granted LCZ696 priority review" said Tim Maloney, President of Novartis Pharmaceuticals Canada Inc. "We look forward to cooperating with Health Canada in its review of the file and to making LCZ696 available to Canadian patients as soon as possible."

The application for priority review by Health Canada was based on a preliminary review of results from the landmark PARADIGM-HF study, the largest ever conducted in heart failure, which compared LCZ696 to the standard care with the ACE-inhibitor enalapril, and showed a 20 per cent reduction of risk in the LCZ696 group on the primary endpoint, a composite measure of cardiovascular death or heart failure hospitalization (p=0.0000002)⁹.

LCZ696 has been granted similar review status in other jurisdictions, including accelerated assessment by the European Union Committee for Medicinal Products for Human Use (CHMP)¹⁰ and priority review by the U.S. Food and Drug Administration¹¹.

About LCZ696 in heart failure
LCZ696, a twice-a-day medicine being investigated for heart failure, has a unique mode of action which is thought to reduce the strain on the failing heart¹². It acts to enhance the protective neurohormonal systems of the heart (NP system) while simultaneously suppressing the harmful system (RAAS).¹³

About heart failure in Canada
Heart failure is a debilitating and life-threatening disease in which the heart cannot pump enough blood around the body. Symptoms such as breathlessness, fatigue and fluid retention can appear slowly and worsen over time, significantly impacting quality of life¹⁴. More than 500,000 Canadians have heart failure¹⁵ and it is responsible for 9 per cent of all deaths in Canada¹⁶ which is almost equal to the number of deaths from breast, colorectal, prostate and pancreatic cancer combined.¹⁷ It is the second leading cause of hospitalization in Canada for patients over 65¹⁸ and resulted in estimated direct costs of $1.18 billion in 2010¹⁹.

Disclaimer
The foregoing release contains forward-looking statements that can be identified by words such as "will, aim, look forward" or similar terms, or by express or implied discussions regarding potential marketing approvals for LCZ696, or regarding potential future revenues from LCZ696. 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 LCZ696 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 LCZ696 will receive regulatory approval or be commercially successful in the future. In particular, management's expectations regarding LCZ696 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 Pharmaceuticals Canada Inc.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 Pharmaceuticals Canada Inc.
Novartis Pharmaceuticals Canada Inc., a leader in the healthcare field, is committed to the discovery, development and marketing of innovative products to improve the well-being of all Canadians. In 2013, the company invested close to $100 million in research and development in Canada. Novartis Pharmaceuticals Canada Inc. employs more than 600 people in Canada. For further information, please consult www.novartis.ca.

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 and cost-saving generic pharmaceuticals. Novartis is the only global company with leading positions in these areas. In 2014, the Group achieved net sales of USD 58 billion, while R&D throughout the Group amounted to approximately USD 9.9 billion (USD 9.6 billion excluding impairment and amortization charges). As of December 31, 2014 Novartis Group companies employed approximately 133,000 full-time-equivalent associates. Novartis products are available in more than 180 countries around the world. For more information, please visit http://www.novartis.com.

References
¹ McMurray JJV, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993-1004. doi: 10.1056/NEJMoa1409077.
² Heart and Stroke Foundation of Canada, Getting to the Heart of the Matter, 2015 Report on the Health of Canadians, page 10. Accessed at: http://www.heartandstroke.com/atf/cf/%7B99452d8b-e7f1-4bd6-a57d-b136ce6c95bf%7D/HSF-2015-HEART-MONTH-REPORT-V2.PDF?utm_campaign=15-HEART&utm_medium=social&utm_source=facebook&utm_content=photo_hm_1_hmrc_en
³ Canadian Heart Failure Network, Rationale for HF Clinics – The Problem: HF, accessed at: http://www.chfn.ca/clinic-resource-manual/rationale-for-hf-clinics citing Brophy JM. Epidemiology of congestive heart failure: Canadian data from 1970 to 1989. Can J Cardiol 1992;8:495-498.
⁴ Canadian Cancer Society's Advisory Committee on Cancer Statistics. Canadian Cancer Statistics 2014, p. 45, Toronto: Canadian Cancer Society; 2014, at: http://www.cancer.ca/en/cancer-information/cancer-101/canadian-cancer-statistics-publication/?region=qc
⁵ Health Canada, Guidance for Industry, Priority Review of Drug Submissions, Ottawa, September 16, 2002, updated December 18, 2008, page 2, accessed at:
http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/prodpharma/priordr-eng.pdf
⁶ Canadian Heart Failure Network, Rationale for HF Clinics – The Problem: HF, accessed at: http://www.chfn.ca/clinic-resource-manual/rationale-for-hf-clinics citing Brophy JM. Epidemiology of congestive heart failure: Canadian data from 1970 to 1989. Can J Cardiol 1992;8:495-498.
⁷ Canadian Institute for Health Information (CIHI), A Snapshot of Health in Canada as Demonstrated by Top 10 Lists, 2011, p. 10, accessed at:
https://secure.cihi.ca/free_products/Top10ReportEN-Web.pdf
⁸ Health Canada, Guidance for Industry, Priority Review of Drug Submissions, Ottawa, September 16, 2002, updated December 18, 2008, page 3, accessed at:
http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/prodpharma/priordr-eng.pdf
⁹ McMurray JJV, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993-1004. doi: 10.1056/NEJMoa1409077.¹⁰ European Medicines Agency. Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 17-20 November 2014 accessed at: http://www.ema.europa.eu/docs/en_GB/document_library/Annex_to_CHMP_highlights/2014/11/WC500177877.pdf 
¹¹ Novartis International AG, Media Release, "Novartis' heart failure medicine LCZ696 granted FDA priority review," Feb. 13, 2015, accessed at:
http://www.novartis.com/newsroom/media-releases/en/2015/1894530.shtml
¹² McMurray JJV, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993-1004. doi: 10.1056/NEJMoa1409077.
¹³ Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: A report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines. Circulation. 2013;128:e240-e327;
Langenickel TH, Dole WP. Angiotensin receptor-neprilysin inhibition with LCZ696: a novel approach for the treatment of heart failure. Drug Discovery Today: Therapeutic Strategies. 2012;9(4):e131-e139. doi: 10.1016/j.ddstr.2013.11.002; and
Roger VL, Weston SA, Redfield MM, et al. Trends in heart failure incidence and survival in a community-based population. JAMA. 2004;292:344-350.
¹⁴ Fauci A, Longo D. Disorders of the Heart. Harrison's 'Principles of Internal Medicine. 17th ed. 2008;4:1442-55. 
¹⁵ Heart and Stroke Foundation of Canada, Getting to the Heart of the Matter, 2015 Report on the Health of Canadians, page 10. Accessed at: http://www.heartandstroke.com/atf/cf/%7B99452d8b-e7f1-4bd6-a57d-b136ce6c95bf%7D/HSF-2015-HEART-MONTH-REPORT-V2.PDF?utm_campaign=15-HEART&utm_medium=social&utm_source=facebook&utm_content=photo_hm_1_hmrc_en
¹⁶ Canadian Heart Failure Network, Rationale for HF Clinics – The Problem: HF, accessed at: http://www.chfn.ca/clinic-resource-manual/rationale-for-hf-clinics citing Brophy JM. Epidemiology of congestive heart failure: Canadian data from 1970 to 1989. Can J Cardiol 1992;8:495-498.
¹⁷ Canadian Cancer Society's Advisory Committee on Cancer Statistics. Canadian Cancer Statistics 2014, p. 45, Toronto: Canadian Cancer Society; 2014, at: http://www.cancer.ca/en/cancer-information/cancer-101/canadian-cancer-statistics-publication/?region=qc
¹⁸ Canadian Institute for Health Information (CIHI), A Snapshot of Health in Canada as Demonstrated by Top 10 Lists, 2011, p. 10, accessed at: https://secure.cihi.ca/free_products/Top10ReportEN-Web.pdf
¹⁹ Cook C. et al., The Annual Global Economic Burden of Heart Failure, International Journal of Cardiology (2014), Table 1

SOURCE Novartis Pharmaceuticals Canada Inc.

Novartis Media Relations: Patricia Tiramani, Novartis Pharma Communications, [phone], [email protected]; Jean Kanan, Spectrum Advisors Communications Inc., [phone], [email protected]