Novartis announces JAMA Cardiology publication of data showing Entresto® improves physical and social activity in HFrEF patients versus enalapril

• Post-hoc analysis of PARADIGM-HF published in JAMA Cardiology shows heart failure patients treated with Entresto experience significant improvements in physical and social activities compared to those taking enalapril[1]
   
• The improvement in combined physical and social activity of patients treated with Entresto versus enalapril was equivalent to a difference of nine years of aging[1]
   
• Treatment benefits to health-related quality of life (HRQL) were seen within eight months and persisted at the three-year follow up period[1]

Basel, April 4, 2018 - Novartis today announced that JAMA Cardiology has published results from a post-hoc analysis demonstrating that treatment with Entresto^® (sacubitril/valsartan) significantly improved seven out of 10 types of physical and social activities at eight months in heart failure patients with reduced ejection fraction (HFrEF) versus previous standard of care.[1] The most significant improvements reported were in the ability to carry out household chores and the ability to conduct intimate/sexual relationships. The findings of the analysis are based on data from the PARADIGM-HF trial, the largest clinical trial ever conducted in heart failure.[2]

"Chronic heart failure patients often experience a significant reduction in quality of life, even when compared to other chronic conditions," said Scott Solomon, MD, , Professor of Medicine, Brigham and Women's Hospital, Harvard Medical School, and senior author of the paper. "This analysis shows that treatment with Entresto can reduce limitations in physical and social activities that are important to heart failure patients, helping to preserve their independence, ability to go about their daily lives and maintain personal relationships."

These data examined the effect of treatment with Entresto on 10 activities related to specific physical and social limitations - which are two of the eight key components of health-related quality of life (HRQL) assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) - as reported by 7,623 patients enrolled in the PARADIGM-HF trial.[1] Treatment with Entresto improved seven out of 10 of these activities at the pre-specified eight month analysis when compared with ACE inhibitor enalapril, with the most significant improvements reported in ability to carry out household chores and ability to conduct intimate/sexual relationships.[1] The improvement in combined physical and social activity of patients treated with Entresto versus enalapril was equivalent to a difference of nine years of aging.[1] Importantly, the physical and social improvements were observed  from the eight-month visit, and were sustained during the study's three-year follow up period.[1]

"These results add to the growing body of evidence that, beyond reducing the risk of death and hospitalization, Entresto has a positive impact on the quality of life of heart failure patients," said Shreeram Aradhye, Chief Medical Officer and Global Head, Medical Affairs, Novartis Pharmaceuticals. "Additionally, as the majority of patients in the PARADIGM-HF study were in the earlier stages of heart failure - NYHA class II - these data are an encouraging indication that Entresto may improve clinically important measures of quality of life, even in patients who do not yet suffer from the more severe symptoms of heart failure."

KCCQ is a self-administered HRQL measure specifically developed and validated for heart failure patients, with higher scores indicating fewer symptoms.[3] This analysis explored the effects on treatment with Entresto on dressing, showering, climbing a flight of stairs, walking 100 yards, visiting family or friends, jogging, gardening, hobbies, doing household chores and intimate/sexual relationships. In PARADIGM-HF, Entresto was shown to reduce the risk of cardiovascular death or first heart failure hospitalization compared with enalapril.[2]

These data were previously presented at the Heart Failure Society of America (HFSA) 21^st Annual Scientific Meeting in Grapevine, Texas in September 2017. 

About Heart Failure
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 heart failure with reduced ejection fraction (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, which accounts for both direct and indirect costs.[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^® (sacubitril/valsartan) 
Entresto is a twice-a-day medicine that reduces the strain on the failing heart. It does this by enhancing the protective neurohormonal systems (natriuretic peptide system) while simultaneously inhibiting the harmful effects of the overactive renin-angiotensin-aldosterone system (RAAS).[10],[11] Other common heart failure medicines, called angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), only block the harmful effects of the overactive RAAS.[12] Entresto contains the neprilysin inhibitor sacubitril and the angiotensin receptor blocker (ARB) valsartan.[10]

In Europe, Entresto is indicated in adult patients for the treatment of symptomatic chronic heart failure with reduced ejection fraction.[10] In the United States, Entresto is indicated for the treatment of heart failure (New York Heart Association class II-IV) in patients with systolic dysfunction.[10] 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.[2] Entresto is usually administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other angiotensin receptor blocker (ARB).[10] Approved indications may vary depending upon the individual country.

Disclaimer
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as "potential," "can," "will," "plan," "expect," "anticipate," "look forward," "believe," "committed," "investigational," "pipeline," "launch," or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations 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 the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political and economic conditions; safety, quality or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, 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, cost-saving generic and biosimilar pharmaceuticals and eye care. Novartis has leading positions globally in each of these areas. In 2017, the Group achieved net sales of USD 49.1 billion, while R&D throughout the Group amounted to approximately USD 9.0 billion. Novartis Group companies employ approximately 122,000 full-time-equivalent associates. Novartis products are sold in approximately 155 countries around the world. For more information, please visit http://www.novartis.com.

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References

      [1]    Chandra, A, Lewis, EF, Claggett, BL, et al. The Effects of Sacubitril/Valsartan on Physical and Social Activity Limitations in Heart Failure Patients: The PARADIGM-HF Trial. JAMA Cardiol. 2018.
      [2]    McMurray JJ, Packer M, Desai AS, Gong J, 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;16:817-825. 
      [3]    Green CP, Porter CB, Bresnahan DR. Development and Evaluation of the Kansas City Cardiomyopathy Questionnaire: A New Health Status Measure for Heart Failure. J Am Coll Cardiol. 2000;35:1245-55.
      [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; 386(9995):743-800.
      [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; 133:e38-e360.
      [6]    Weir 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]    American Heart Association. Ejection Fraction Heart Failure Measurement. Available at: http://www.heart.org/HEARTORG/Conditions/HeartFailure/SymptomsDiagnosisofHeartFailure/Ejection-Fraction-Heart-Failure-Measurement_UCM_306339_Article.jsp. Last accessed: March 2017.
      [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]  Langenickel T, Dole W. Angiotensin receptor-neprilysin inhibition with LCZ696: a novel approach for the treatment of heart failure. Drug Disc Today. 2012; 4:131-139.
      [12]  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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