Welcome!

News Feed Item

Novartis' new heart failure medicine LCZ696 cut cardiovascular deaths by 20% vs. ACE-inhibitor in landmark PARADIGM-HF trial

- Study showed significantly more HF-REF patients on LCZ696 regimen were alive, had fewer hospitalizations than those given enalapril regimen(1)

EAST HANOVER, N.J., Aug. 30, 2014 /PRNewswire/ -- Today at the European Society of Cardiology congress and published simultaneously in the New England Journal of Medicine, Novartis revealed that its investigational heart failure medicine, LCZ696, was superior to ACE-inhibitor enalapril on key endpoints in the largest heart failure study ever done.1,7 In PARADIGM-HF, patients with heart failure with reduced ejection fraction (HF-REF) who were given LCZ696 were more likely to be alive and less likely to have been hospitalized for sudden deterioration of their heart failure than those given ACE-inhibitor enalapril.1 Patients received LCZ696 or enalapril on top of current best treatment.7

To view the multimedia assets associated with this release, please click http://www.multivu.com/players/English/7282951-novartis-lcz696-reduced-risk-cardiovascular-death-hospitalization-heart-patients/

The magnitude of benefit with LCZ696 against enalapril in HF-REF patients was highly statistically significant and clinically important. In the study, the benefit of LCZ696 was seen early, was sustained and was consistent across subgroups. LCZ696:1

  • reduced the risk of death from cardiovascular (CV) causes by 20% (p=0.00004)
  • reduced heart failure hospitalizations by 21% (p=0.00004)
  • reduced the risk of all-cause mortality by 16% (p=0.0005)

Overall there was a 20% risk reduction on the primary endpoint, a composite measure of CV death or heart failure hospitalization (p=0.0000002).1

"By demonstrating a very significant reduction in cardiovascular deaths while improving quality of life, Novartis' new heart failure medicine, LCZ696, represents one of the most important cardiology advances of the last decade," said David Epstein, Division Head, Novartis Pharmaceuticals. "We want to thank leading cardiologists from around the world for their collaboration with us and their determination in advancing this important new life saving therapy for heart failure patients."

LCZ696, a twice a day tablet being investigated for heart failure, has a unique mode of action which is thought to reduce the strain on the failing heart.7,8 It acts to enhance the protective neurohormonal systems of the heart (NP system) while simultaneously suppressing the harmful effects of the overactive RAAS (renin-angiotensin-aldosterone system).7,8 Currently available medicines for HF-REF work only to block the detrimental effects.9 Despite existing therapies, the mortality rate remains very high with up to 50% of patients dying within 5 years of a diagnosis of heart failure.3 Approximately half of patients with heart failure have HF-REF.10

Analysis of the safety data from PARADIGM-HF showed side effects were manageable in the study.1 Fewer patients on LCZ696 discontinued study medication for any adverse event compared to those on enalapril (10.7% vs. 12.3%, respectively; p=0.03). The LCZ696 group had more hypotension and non-serious angioedema but less renal impairment, hyperkalemia and cough than the enalapril group. The most common adverse events with LCZ696 (incidence ≥10%) compared to enalapril were elevated serum potassium of more than 5.5 mmol/liter (16.1% vs. 17.3%), symptomatic hypotension (14.0% vs. 9.2%) and cough (11.3% vs. 14.3%).1

Novartis plans to file the New Drug Application for review with the US FDA by the end of 2014.

About the PARADIGM-HF study

PARADIGM-HF is a randomized, double-blind, Phase III study evaluating the efficacy and safety profile of LCZ696 versus enalapril (a widely studied ACE-inhibitor) in 8,442 patients with HF-REF.7,11,12 The baseline characteristics showed the patients enrolled were typical HF-REF patients with NYHA Class II-IV heart failure.11 PARADIGM-HF was specifically designed to see if LCZ696 could decrease CV mortality by at least 15% vs. enalapril.7 Patients received LCZ696 or enalapril in addition to current best treatment regimen. The primary endpoint is a composite of time to first occurrence of either cardiovascular death or heart failure hospitalization, and the trial is the largest heart failure study ever done.7

Secondary endpoints are change in the clinical summary score for heart failure symptoms and physical limitations (as assessed by Kansas City Cardiomyopathy Questionnaire) at 8 months; time to all-cause mortality; time to new onset atrial fibrillation; and time to occurrence of renal dysfunction.7 PARADIGM-HF was initiated in December 2009, and in March 2014 the Data Monitoring Committee confirmed that patients given LCZ696 were significantly less likely to die from CV causes, and that the primary endpoint was met, leading to the trial being stopped early.13

About LCZ696 in heart failure

LCZ696 is an ARNI (Angiotensin Receptor Neprilysin Inhibitor) and has a unique mode of action which is thought to reduce the strain on the failing heart.7,8 It acts to enhance the protective neurohormonal systems of the heart (NP system) while simultaneously suppressing the effects of the overactive renin-angiotensin-aldosterone system (RAAS).7,8

Heart failure is a debilitating and potentially 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.4

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.3

Disclaimer

The foregoing release contains forward-looking statements that can be identified by words such as "being investigated," "thought," "plans," "growing," "mission," 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 approved for sale in any market, or submitted for approval in any additional markets, or at any particular time. Neither can there be any 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 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 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, cost-saving generic pharmaceuticals, preventive vaccines, over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 2013, the Group achieved net sales of USD 57.9 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 135,000 full-time-equivalent associates and sell products in more than 150 countries around the world. For more information, please visit http://www.novartis.com.

Novartis is on Twitter. Sign up to follow @Novartis at http://twitter.com/novartis.

References:

  1. McMurray JJV, Packer M, Desai AS, et al. Angiotensin-Neprilysin Inhibition versus Enalapril in Heart Failure. N Engl J Med. 2014. doi: 10.1056/NEJMoa1409077.
  2. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991;325:293–302.
  3. Go A, Mozaffarian D, Roger V, et al. Heart Disease and Stroke Statistics−−2014 Update: A Report From the American Heart Association. Circulation. 2014;4(129):e28-e292.
  4. Fauci A and Longo D. Disorders of the Heart. Harrison's 'Principles of Internal Medicine. 17th ed. 2008;4:1442-55.
  5. Junger J, Schellberg D, Kraemer S, et al. Health related quality of life in patients with congestive heart failure: comparison with other chronic diseases and relation to functional variables. Heart. 2002;87(3):235-241.
  6. Levy D, Kenchaiah S, Larson M, et al. Long-Term Trends In The Incidence Of And Survival With Heart Failure. N Engl J Med. 2002;347(18):1397-1402.
  7. McMurray JJ, 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.
  8. Langenickel TH and 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.
  9. 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. doi: 10.1161/CIR.0b013e31829e8776.
  10. Vasan R, Larson M, Benjamin E, et al. Congestive Heart Failure in Subjects with Normal Versus Reduced Left Ventricle Ejection Fraction. J Am Coll Cardiol. 1999;33(7):1948-1955. 
  11. McMurray JJ, 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;16:817-825.
  12. Clinicaltrials.gov. This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure (PARADIGM-HF). NCT01035255. http://clinicaltrials.gov/show/NCT01035255. Accessed August 2014.
  13. Novartis. PARADIGM-HF trial of Novartis' LCZ696 for chronic heart failure closes early based on strength of interim results. Novartis U.S. Newsroom. March 31, 2014. http://www.novartis.com/newsroom/media-releases/en/2014/1772754.shtml. Accessed July 2014.

 

 

Novartis Media Relations


Julie Masow

Michael Billings

Novartis Media Relations

Novartis Pharmaceuticals Corporation

+1 212 830 2465 (direct)

+1 862 778 8656 (direct)

+1 862 579 8456 (mobile)

+1 201 400 1854 (mobile)

[email protected] 

[email protected]



e-mail: [email protected] 


 

For Novartis multimedia content, please visit www.thenewsmarket.com/Novartis.

For questions about the site or required registration, please contact: [email protected].

 

SOURCE Novartis Pharmaceuticals Corporation

More Stories By PR Newswire

Copyright © 2007 PR Newswire. All rights reserved. Republication or redistribution of PRNewswire content is expressly prohibited without the prior written consent of PRNewswire. PRNewswire shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon.

Latest Stories
DX World EXPO, LLC, a Lighthouse Point, Florida-based startup trade show producer and the creator of "DXWorldEXPO® - Digital Transformation Conference & Expo" has announced its executive management team. The team is headed by Levent Selamoglu, who has been named CEO. "Now is the time for a truly global DX event, to bring together the leading minds from the technology world in a conversation about Digital Transformation," he said in making the announcement.
"Space Monkey by Vivent Smart Home is a product that is a distributed cloud-based edge storage network. Vivent Smart Home, our parent company, is a smart home provider that places a lot of hard drives across homes in North America," explained JT Olds, Director of Engineering, and Brandon Crowfeather, Product Manager, at Vivint Smart Home, in this SYS-CON.tv interview at @ThingsExpo, held Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA.
DevOps is under attack because developers don’t want to mess with infrastructure. They will happily own their code into production, but want to use platforms instead of raw automation. That’s changing the landscape that we understand as DevOps with both architecture concepts (CloudNative) and process redefinition (SRE). Rob Hirschfeld’s recent work in Kubernetes operations has led to the conclusion that containers and related platforms have changed the way we should be thinking about DevOps and...
SYS-CON Events announced today that Conference Guru has been named “Media Sponsor” of the 22nd International Cloud Expo, which will take place on June 5-7, 2018, at the Javits Center in New York, NY. A valuable conference experience generates new contacts, sales leads, potential strategic partners and potential investors; helps gather competitive intelligence and even provides inspiration for new products and services. Conference Guru works with conference organizers to pass great deals to gre...
The Internet of Things will challenge the status quo of how IT and development organizations operate. Or will it? Certainly the fog layer of IoT requires special insights about data ontology, security and transactional integrity. But the developmental challenges are the same: People, Process and Platform. In his session at @ThingsExpo, Craig Sproule, CEO of Metavine, demonstrated how to move beyond today's coding paradigm and shared the must-have mindsets for removing complexity from the develop...
In his Opening Keynote at 21st Cloud Expo, John Considine, General Manager of IBM Cloud Infrastructure, led attendees through the exciting evolution of the cloud. He looked at this major disruption from the perspective of technology, business models, and what this means for enterprises of all sizes. John Considine is General Manager of Cloud Infrastructure Services at IBM. In that role he is responsible for leading IBM’s public cloud infrastructure including strategy, development, and offering m...
Companies are harnessing data in ways we once associated with science fiction. Analysts have access to a plethora of visualization and reporting tools, but considering the vast amount of data businesses collect and limitations of CPUs, end users are forced to design their structures and systems with limitations. Until now. As the cloud toolkit to analyze data has evolved, GPUs have stepped in to massively parallel SQL, visualization and machine learning.
The next XaaS is CICDaaS. Why? Because CICD saves developers a huge amount of time. CD is an especially great option for projects that require multiple and frequent contributions to be integrated. But… securing CICD best practices is an emerging, essential, yet little understood practice for DevOps teams and their Cloud Service Providers. The only way to get CICD to work in a highly secure environment takes collaboration, patience and persistence. Building CICD in the cloud requires rigorous ar...
"Evatronix provides design services to companies that need to integrate the IoT technology in their products but they don't necessarily have the expertise, knowledge and design team to do so," explained Adam Morawiec, VP of Business Development at Evatronix, in this SYS-CON.tv interview at @ThingsExpo, held Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA.
To get the most out of their data, successful companies are not focusing on queries and data lakes, they are actively integrating analytics into their operations with a data-first application development approach. Real-time adjustments to improve revenues, reduce costs, or mitigate risk rely on applications that minimize latency on a variety of data sources. In his session at @BigDataExpo, Jack Norris, Senior Vice President, Data and Applications at MapR Technologies, reviewed best practices to ...
Widespread fragmentation is stalling the growth of the IIoT and making it difficult for partners to work together. The number of software platforms, apps, hardware and connectivity standards is creating paralysis among businesses that are afraid of being locked into a solution. EdgeX Foundry is unifying the community around a common IoT edge framework and an ecosystem of interoperable components.
"ZeroStack is a startup in Silicon Valley. We're solving a very interesting problem around bringing public cloud convenience with private cloud control for enterprises and mid-size companies," explained Kamesh Pemmaraju, VP of Product Management at ZeroStack, in this SYS-CON.tv interview at 21st Cloud Expo, held Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA.
Large industrial manufacturing organizations are adopting the agile principles of cloud software companies. The industrial manufacturing development process has not scaled over time. Now that design CAD teams are geographically distributed, centralizing their work is key. With large multi-gigabyte projects, outdated tools have stifled industrial team agility, time-to-market milestones, and impacted P&L stakeholders.
"Akvelon is a software development company and we also provide consultancy services to folks who are looking to scale or accelerate their engineering roadmaps," explained Jeremiah Mothersell, Marketing Manager at Akvelon, in this SYS-CON.tv interview at 21st Cloud Expo, held Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA.
Enterprises are adopting Kubernetes to accelerate the development and the delivery of cloud-native applications. However, sharing a Kubernetes cluster between members of the same team can be challenging. And, sharing clusters across multiple teams is even harder. Kubernetes offers several constructs to help implement segmentation and isolation. However, these primitives can be complex to understand and apply. As a result, it’s becoming common for enterprises to end up with several clusters. Thi...