Novartis' Heart Failure Medicine LCZ696 Granted FDA Priority Review

• Decision could speed access to LCZ696 for heart failure with reduced ejection fraction patients in the US, reducing total review time from 12 to 8 months¹
• Filing is based on results from the landmark PARADIGM-HF study²
• Nearly six million people live with heart failure in the US, and despite current therapies, up to 50% of patients die within five years of diagnosis^3,4

Novartis announced recently that the US Food and Drug Administration (FDA) has granted priority review for LCZ696, an investigational medicine for the treatment of heart failure with reduced ejection fraction (HFrEF). The designation is intended to accelerate the review of therapies that offer a significant improvement in the safety or effectiveness of the treatment, prevention or diagnosis of a serious condition.⁵ For LCZ696, this reduces the total review time from 12 to 8 months, meaning the target FDA action date is in August 2015.¹

“The FDA’s decision to grant priority review brings us one step closer to making this promising treatment available to the millions of Americans who are struggling with this debilitating condition,” said Christi Shaw, US Country Head, President of Novartis Corporation and President of Novartis Pharmaceuticals Corporation. “LCZ696 has the potential to change the way that many heart failure patients are treated in this country, giving them and their loved ones greater hope for their future.”

The New Drug Application (NDA) is based on results from the landmark PARADIGM-HF study, the largest ever conducted in heart failure.⁶ The study showed LCZ696 was superior to the accepted guideline therapy ACE-inhibitor enalapril on key endpoints, including the primary endpoint, which showed reduction of the risk of either cardiovascular death or heart failure hospitalization by 20%.^2,7

In the European Union, the Committee for Medicinal Products for Human Use (CHMP) has granted accelerated assessment to LCZ696.⁸

About LCZ696 in heart failure
LCZ696, a twice-a-day medicine being investigated for heart failure, acts to enhance the protective neurohormonal systems of the heart (NP system) while simultaneously suppressing the harmful effects of the overactive renin-angiotensin-aldosterone system (RAAS). Currently available medicines for heart failure with reduced ejection fractiononly block the harmful effects and mortality remains very high, with up to 50% of patients dying within 5 years of a diagnosis of heart failure.^4,7,9

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 life.¹⁰

It represents a major and growing health-economic burden that currently exceeds $30B in the United States, accounting for both direct and indirect costs. Hospitalizations account for 80% of the $21B spent on the direct costs of heart failure.¹¹

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, cost-saving generic pharmaceuticals, preventive vaccines and over-the-counter products. 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). Novartis Group companies employ approximately 130,000 full-time-equivalent associates. Novartis products are available in more than 180 countries around the world. For more information, visit http://www.novartis.com.

References
¹. U.S. Food and Drug Administration Center for Drug Evaluation and Research (CDER). CDER 21st Century Review Process Desk Reference Guide: New Drug Application and Biologics License Application Reviews.http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDER/ManualofPoliciesProcedures/UCM218757.htm. Updated September 2014. Accessed February 5, 2015.

². 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.

³. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart Disease and Stroke Statistics – 2015 Update: A Report from the American Heart Association. Circulation. 2015;131:00-00.

⁴. 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.

⁵. U.S. Food and Drug Administration. Priority Review. http://www.fda.gov/ForPatients/Approvals/Fast/ucm405405.htm. Updated September 15, 2014. Accessed January 27, 2015.

⁶. McMurray JJV, Packer M, Desai AS, et al. Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF). Eur J Heart Fail. 2013;15:1062-73. doi:10.1093/eurjhf/hft052.

⁷. 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.

⁸. Novartis. Novartis' heart failure medicine LCZ696 granted accelerated assessment by CHMP in Europe[1]. Novartis Newsroom.http://www.novartis.com/newsroom/media-releases/en/2014/1874782.shtml. Published November 28, 2014. Accessed January 27, 2015.

⁹. 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.

¹⁰. Fauci A, Longo D. Disorders of the Heart. Harrison’s Principles of Internal Medicine. 17th ed. New York, NY; McGraw-Hill Book Co. 2008;4:1442-55.

¹¹. 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(3):606-619.