Novartis' Entresto® given strong Class I recommendation in both US and EU heart failure guidelines, less than a year after regulatory approvals

• US guidelines now recommend Entresto as standard of care for HFrEF as an alternative to ACEs or ARBs; call for doctors to switch patients with mild to moderate symptoms to Entresto[1]
   
• Updated guidelines from the European Society of Cardiology recommend Entresto instead of an ACE or ARB in patients fitting the PARADIGM-HF profile[2]
   
• Guidance underscores the benefits of Entresto for patients to significantly reduce risk of death due to cardiovascular causes or heart failure hospitalization

Basel, May 21, 2016 - Entresto^® (sacubitril/valsartan) has been given a Class I recommendation, the strongest endorsement, in updated clinical practice guidelines simultaneously released by the American College of Cardiology (ACC), the American Heart Association (AHA) and the Heart Failure Society of America (HFSA) in the US, and the European Society of Cardiology in the EU.

In the US Entresto is now a standard therapy for heart failure with reduced ejection fraction (HFrEF) as an alternative to an ACE inhibitor or an angiotensin II receptor blocker, given together with a beta blocker and an aldosterone antagonist. In addition, the guidelines call for doctors to switch HFrEF patients with mild to moderate symptoms from ACEs or ARBs to Entresto.

"These strong, swift and broad recommendations by US cardiology organizations, redefine the standard of care for how reduced ejection fraction heart failure is treated," said Vas Narasimhan, Global Head of Development and Chief Medical Officer for Novartis. "We know patients with heart failure suffer reduced quality of life and remain at high risk of hospitalization or death, and these new guidelines are a strong call to action to ensure patients receive the most effective therapies."

In the EU, the ESC HF guidelines recommend doctors switch HFrEF patients meeting the PARADIGM-HF criteria to Entresto from an ACE or ARB. Both guideline committees considered evidence from PARADIGM-HF, the largest heart failure trial ever, which showed Entresto significantly reduced deaths from cardiovascular causes and heart failure hospitalizations in patients with HFrEF[3].

Heart failure is a debilitating and life-threatening condition, which impacts over 60 million people worldwide[4]. It is the leading cause of hospitalization in people over the age of 65[5],[6]. About half of people with heart failure have HFrEF[7]. Reduced ejection fraction means the heart does not contract with enough force, so less blood is pumped out[8]. Heart failure presents a major and growing health-economic burden that currently costs the world economy $108 billion every year[5],[9].

Novartis has established the largest global clinical program in the heart failure disease area across the pharma industry to date, FortiHFy, comprising over 40 active or planned clinical studies designed to generate an array of additional data on symptom reduction, efficacy, quality of life benefits and real world evidence with Entresto, as well as to extend understanding of heart failure.

About Entresto
Entresto is a twice-a-day medicine that reduces the strain on the failing heart. It does this by enhancing the protective neurohormonal systems of the heart (NP system) while simultaneously suppressing the harmful effects of the overactive renin-angiotensin-aldosterone system (RAAS)[10]. Other heart failure medicines only block the harmful effects of the overactive RAAS[11]. Entresto contains the neprilysin inhibitor sacubitril and the angiotensin receptor blocker (ARB) valsartan[10].

In Europe, Entresto is indicated in adult patients for treatment of symptomatic chronic heart failure with reduced ejection fraction. In the U.S. Entresto is indicated for the treatment of heart failure (NYHA class II-IV) in patients with systolic dysfunction. It has been shown to reduce the rate of cardiovascular death and heart failure hospitalization compared to enalapril, and also to reduce the rate of all-cause mortality compared to enalapril. Entresto is usually administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other angiotensin receptor blocker (ARB). Approved indications may vary depending upon the individual country.

About PARADIGM-HF
PARADIGM-HF was a randomized, double-blind, phase III study evaluating the efficacy and safety profile of Entresto versus enalapril (a widely studied ACE inhibitor) in 8,442 patients with HFrEF. The baseline characteristics showed the patients enrolled were typical HFrEF patients with NYHA Class II-IV heart failure. PARADIGM-HF was specifically designed to see if LCZ696 could decrease CV mortality by at least 15% vs. enalapril. Patients received LCZ696 or enalapril in addition to current best treatment regimen. The primary endpoint was a composite of time to first occurrence of either cardiovascular death or heart failure hospitalization, and is the largest heart failure study ever done.

Disclaimer
The foregoing release contains forward-looking statements that can be identified by words such as "recommendation," "guidelines," "recommend," "call for," "guidance," "call to action," "recommend," "growing," "planned," "designed to," or similar terms, or by express or implied discussions regarding potential new indications or labeling for Entresto, or regarding potential future revenues from Entresto. 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 Entresto 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 Entresto will be commercially successful in the future. In particular, management's expectations regarding Entresto 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 safety, quality or 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 and cost-saving generic pharmaceuticals. Novartis is the only global company with leading positions in these areas. In 2015, the Group achieved net sales of USD 49.4 billion, while R&D throughout the Group amounted to approximately USD 8.9 billion (USD 8.7 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 118,000 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.

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References
[1] https://content.onlinejacc.org/article.aspx?articleid=2524644
[2] 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal. doi:10.1093/eurheartj/ehw128
[3] McMurray JJV et al. Angiotensin-Neprilysin Inhibition versus Enalapril in Heart Failure, N Engl J Med 2014.
[4] Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013, Lancet 2015.
[5] Mozaffarian D, Benjamin EJ, Go AS, et al. Heart Disease and Stroke Statistics-2016 Update: A report from the American Heart Association. Circulation. 2015; 132:000-000. doi: 10.1161/CIR.0000000000000350.
[6] Wier LM, Pfuntner A, Maeda J, et al. HCUP facts and figures: statistics on hospital-based care in the United States, 2009. Rockville, MD: Agency for Healthcare Research and Quality, 2011.
[7] Owan TE, Hodge DO, Herges RM, et al. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006;355:251-259.
[8] Ejection Fraction Heart Failure Measurement. American Heart Association Website. http://www.heart.org/HEARTORG/Conditions/HeartFailure/SymptomsDiagnosisofHeartFailure/Ejection-Fraction-Heart-Failure-Measurement_UCM_306339_Article.jsp. Published March 24, 2015. Accessed March 10, 2016.
[9] Heidenreich PA, Albert NM, Allen LA, et al. Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association. Circ Heart Fail. 2013;6:606-619.
[10] Entresto Prescribing Information.
[11] 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.

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