New analyses show Novartis' Entresto™ reduced cardiovascular death or hospitalization for heart failure, consistently benefitting patients with reduced ejection fraction (HFrEF) regardless of prior heart failure hospital admissions or background therapy

EAST HANOVER, N.J., April 2, 2016 /PRNewswire/ -- Novartis announced today new post-hoc analyses that underscore the clinical benefits of Entresto^™ (sacubitril/valsartan) tablets compared to enalapril among heart failure patients with reduced ejection fraction (HFrEF), irrespective of patients' clinical stability or background therapy.^1,2 The analyses are of data from PARADIGM-HF, the largest clinical trial ever conducted in heart failure which compared Entresto to ACE inhibitor enalapril,³ and are being presented at the American College of Cardiology's 65^th Annual Scientific Session in Chicago.

"In PARADIGM-HF, about half of primary events among stable patients were cardiovascular death.¹ This indicates that the full spectrum of patient types we studied in the trial may be at risk for adverse outcomes due to the disease," said Scott Solomon, MD, Director of Noninvasive Cardiology, Brigham and Women's Hospital and Professor of Medicine, Harvard Medical School. "In fact, the analyses make a case that patients we consider clinically stable, as well as those who are already being treated with guideline-directed background therapy may benefit from sacubitril/valsartan."^1,2

For many cardiovascular (CV) conditions, including heart failure, the clinical stability of patients may influence treatment and management decisions. An analysis of PARADIGM-HF patients found that even patients considered to be clinically stable – defined as patients with no history or only a remote history of prior heart failure hospitalization – were still at risk for a serious clinical event.¹ In the analysis, over one third of patients were identified as clinically stable, and 20% of those experienced a primary endpoint event (CV death or heart failure hospitalization).¹ Among these patients, 51% suffered CV death as their first event.¹ Further, the analysis determined that Entresto benefited patients who were considered clinically stable just as much as it did those who were least-stable (heart failure hospitalization within 3 months of baseline).¹ Among both groups, patients taking Entresto had a 20% or greater reduction in CV death or heart failure hospitalization compared to those taking enalapril.¹

In the second analysis, Entresto showed consistent benefits among HFrEF patients, reducing the risk of CV death or heart failure hospitalization by approximately 20% compared to enalapril, regardless of background therapy.² These benefits were observed for Entresto among patients taking higher and lower doses of beta blockers and those with or without an implantable cardioverter-defibrillator (ICD) or a cardiac resynchronization therapy defibrillator (CRT-D) – two commonly used treatment approaches for heart failure – as well as mineralocorticoid receptor antagonists (MRAs).²

"We're encouraged by these new analyses for Entresto. The positive results add to the already robust evidence that shows the potential benefits this medicine can offer heart failure patients with reduced ejection fraction," said Christi Shaw, US Country Head, President of Novartis Corporation and Novartis Pharmaceuticals Corporation. "What's important is that these data can translate into real-world impact by giving doctors, nurses and other healthcare providers a much needed medicine to help more of their patients better manage this debilitating and life-threatening condition."

About Heart Failure
Heart failure is a debilitating and life-threatening condition, which impacts nearly 6 million Americans and is the leading cause of hospitalization among Americans over the age of 65.^4,5 About half of people with heart failure have heart failure with reduced ejection fraction (HFrEF).⁶ Reduced ejection fraction means the heart does not contract with enough force, so less blood is pumped out.⁷ Heart failure presents a major and growing health-economic burden that currently exceeds $30 billion in the United States, which accounts for both direct and indirect costs.⁸

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).⁹ Other heart failure medicines only block the harmful effects of the overactive RAAS.¹⁰ Entresto contains the neprilysin inhibitor sacubitril, which is a new molecular entity, and the angiotensin receptor blocker (ARB) valsartan.⁹

Entresto is indicated in the US to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.⁹ Entresto is usually administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other angiotensin receptor blocker (ARB). Entresto film-coated tablets are available in three dosage strengths: 24/26 mg, 49/51 mg, and 97/103 mg (sacubitril/valsartan).⁹ These doses are referred to as 50 mg, 100 mg, and 200 mg in the clinical trial literature including the New England Journal of Medicine publication of the results of PARADIGM-HF. The target treatment dose of Entresto is 97/103 mg twice daily.⁹

Novartis is committed to providing patients with affordable access and resources through Entresto Central. For more information, please call 1-888-ENTRESTO or visit www.entresto.com.

Please visit http://www.pharma.us.novartis.com/product/pi/pdf/entresto.pdf for Entresto full Prescribing Information.

IMPORTANT SAFETY INFORMATION
Entresto can harm or cause death to an unborn baby. Patients should talk to their doctor about other ways to treat heart failure if they plan to become pregnant. If a patient gets pregnant while taking Entresto, she should tell her doctor right away.

Patients are not to take Entresto if they are allergic to sacubitril or valsartan or any of the ingredients in Entresto; have had an allergic reaction including swelling of the face, lips, tongue, throat or trouble breathing while taking a type of medicine called angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB); or take an ACE inhibitor medicine. Patients are not to take Entresto for at least 36 hours before or after they take an ACE inhibitor medicine. Patients should talk with their doctor or pharmacist before taking Entresto if they are not sure if they take an ACE inhibitor medicine.  Patients are not to take Entresto if they have diabetes and take a medicine that contains aliskiren.

Before they take Entresto, patients should tell their doctor about all of their medical conditions, including if they have kidney or liver problems; are pregnant or plan to become pregnant; are breastfeeding or plan to breastfeed. Patients should either take Entresto or breastfeed. They should not do both.

Patients should tell their doctor about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. They should especially tell their doctor if they take potassium supplements or a salt substitute; nonsteroidal anti-inflammatory drugs (NSAIDs); lithium; or other medicines for high blood pressure or heart problems such as an ACE inhibitor, ARB, or aliskiren.

Entresto may cause serious side effects including serious allergic reactions causing swelling of the face, lips, tongue, and throat (angioedema) that may cause trouble breathing and death.  Patients are to get emergency medical help right away if they have symptoms of angioedema or trouble breathing. Patients are not to take Entresto again if they have had angioedema while taking Entresto.  People who are black or who have had angioedema may have a higher risk of having angioedema if they take Entresto. Entresto may cause low blood pressure (hypotension). Patients are to call their doctor if they become dizzy or lightheaded, or they develop extreme fatigue. Entresto may cause kidney problems or an increased amount of potassium in the blood.

The most common side effects were low blood pressure, high potassium, cough, dizziness, and kidney problems.

Please see full Prescribing Information, including Boxed WARNING available at http://www.pharma.us.novartis.com/product/pi/pdf/entresto.pdf.

Patients are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Disclaimer
The foregoing release contains forward-looking statements that can be identified by words such as "may," "potential," "can," "committed," 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 issues; unexpected manufacturing or quality 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 Pharmaceuticals Corporation researches, develops, manufactures and markets innovative medicines aimed at improving patients' lives. We offer a broad range of medicines for cancer, cardiovascular disease, endocrine disease, inflammatory disease, infectious disease, neurological disease, organ transplantation, psychiatric disease, respiratory disease and skin conditions. The company's mission is to improve people's lives by pioneering novel healthcare solutions.

Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG, which 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 119,000 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. Solomon S. Efficacy of Sacubitril/Valsartan Relative to a Prior Decompensation in Patients with Heart Failure and Reduced Ejection Fraction: The PARADIGM-HF Trial [poster]. American College of Cardiology's 65th Annual Scientific Session & Expo; Chicago, IL, USA.
2. McMurray JJV. Consistent Benefit of Sacubitril/valsartan Over Enalapril, Irrespective Of Background Therapy In Paradigm-hf [abstract]. American College of Cardiology's 65th Annual Scientific Session & Expo; Chicago, IL, USA. 
3. McMurray JJV, Packer M, Desai AS, et al. Baseline characteristics and treatment of patients in prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial (PARADIGM-HF). Eur J Heart Fail. 2014;16(7):817-25.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. Entresto Prescribing Information.
10. 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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