|By PR Newswire||
|August 30, 2014 11:13 AM EDT||
- LCZ696 mortality benefit exceeded what was achieved with enalapril, an ACE-inhibitor, when replacing enalapril combined with current treatment regimen for HF-REF1
- Study showed significantly more HF-REF patients on LCZ696 regimen were alive and had fewer hospitalizations than those given enalapril regimen1
- Heart failure affects more than 600,000 Canadians18 and is responsible for 9 per cent of all deaths in Canada19 representing an equal prevalence of death from breast, colorectal, prostate and pancreatic cancer combined22.
DORVAL, QC, Aug. 30, 2014 /CNW/ - Today at the European Society of Cardiology congress and published simultaneously in the New England Journal of Medicine, Novartis Pharmaceuticals Canada Inc. revealed, in the largest heart failure study to date,1,5 that its investigational heart failure medicine, LCZ696, was superior to the ACE-inhibitor enalapril on key endpoints. In PARADIGM-HF, patients with heart failure and reduced ejection fraction (HF-REF) who were given LCZ696 were more likely to remain alive and have less re-hospitalization for heart failure than those given the ACE-inhibitor enalapril1. Patients received LCZ696 or enalapril combined with the current best treatment regimen for heart failure treatment. The safety and efficacy of LCZ696 is still under investigation and market authorization has not yet been obtained in Canada.
"The results of the PARADIGM study showed a reduction in hospitalizations for heart failure, a reduction in cardiovascular mortality and a reduction in total mortality when added to optimal therapy. It also improved the quality of life of patients in the trial," said cardiologist Dr. Jean-Lucien Rouleau of the Montreal Heart Institute, a member of the PARADIGM-HF executive committee and a co-author of the study article. "These results are important given that one in every five or six of the Canadian population, over the age of 40 will experience heart failure. The PARADIGM-HF results are promising and may have a major impact in the way we manage heart failure in the future."
The PARADIGM-HF results showed that the investigational treatment LCZ696, when added to current optimal care and compared to adding the ACE-inhibitor enalapril to optimal care: 1
- reduced the risk of death from cardiovascular 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.
"Given the increasing prevalence, the high hospitalization rate and mortality in heart failure, there is a great need for new treatment alternatives in Canada and around the world'' said Dr. Jean Godin, Chief Scientific Officer and Vice-President, Clinical and Regulatory Affairs of Novartis Pharmaceuticals Canada Inc. "These results show the importance of pursuing research and development efforts to further improve the health outcomes of patients affected by this condition."
About LCZ696 in heart failure
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 heart5,6,7. It acts to enhance the protective neurohormonal systems of the heart (NP system) while simultaneously suppressing the RAAS system5,7.
Analysis of the safety data from PARADIGM-HF showed side effects were manageable in the study1. 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.
Novartis plans to pursue filings for marketing authorizations in different jurisdictions around the world starting late in 2014 and continuing in 2015.
About the PARADIGM-HF study
PARADIGM-HF was 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-REF5,12. The baseline characteristics showed that the patients enrolled were typical HF-REF 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. enalapril5. Patients received LCZ696 or enalapril in addition to the current best treatment regimen. The primary endpoint was a composite of time to first occurrence of either cardiovascular death or heart failure hospitalization, and was the largest heart failure study done to date5.
Secondary endpoints included 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 dysfunction5. PARADIGM-HF was initiated in December 2009 and in March 2014 the Data Monitoring Committee (DMC) confirmed that patients given LCZ696 were significantly less likely to die from CV causes, leading to the trial being stopped early13. The DMC also confirmed the primary endpoint had been met.
About heart failure in Canada
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 life3,14. More than 600,000 Canadians have heart failure18 and it is responsible for 9 per cent of all deaths in Canada19 which is almost equal to the number of deaths from breast, colorectal, prostate and pancreatic cancer combined.22 It is the second leading cause of hospitalization in Canada for patients over 6520 and resulted in estimated direct costs of $1.18 billion in 2010.21
The foregoing release contains forward-looking statements that can be identified by words such as "will, aim, look forward" 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 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 receive regulatory approval or 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 Pharmaceuticals Canada Inc.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.
Novartis Pharmaceuticals Canada Inc., a leader in the healthcare field, is committed to the discovery, development and marketing of innovative products to improve the well-being of all Canadians. In 2013, the company invested close to $100 million in research and development in Canada. Novartis Pharmaceuticals Canada Inc. employs more than 600 people in Canada. For further information, please consult www.novartis.ca. Novartis Pharmaceuticals Canada Inc. is a subsidiary of Novartis AG, which provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis Group of Companies offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, preventive vaccines and diagnostic tools, 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 136,000 full-time-equivalent associates and operate in more than 140 countries around the world. For more information, please visit www.novartis.com .
- McMurray JJV et al. Angiotensin-Neprilysin Inhibition versus Enalapril in Heart Failure, N Engl J Med 2014; DOI: 10.1056/NEJMoa1409077
- Ambrosy AP et al. J Am Coll Cardiol 2014;63:1123-33. doi: 10.1016/j.jacc.2013.11.053
- Gheorghiade M, Pang P, Acute heart failure syndromes, Journal of the American College of Cardiology 2009; 53 (7):557-73
- Harrison's 'Principles of Internal Medicine', Seventeenth Edition pages 1442 - 1455
- 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;15,1062-1073 (doi:10.1093/eurjhf/hft052)
- Langenickel TH et al. Angiotensin receptor-neprilysin inhibition with LCZ696: a novel approach for the treatment of heart failure. Drug Discovery Today: Therapeutic Strategies.2012, Vol 9. No.4
- Solomon SD et al. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial. Lancet. 2012;380:1387-95
- Lloyd-Jones et al. Heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation. 2010;121:e46-215
- Zannad F. et al, Heart failure burden and therapy, Europace 2009, 11; v1-v9.
- Loehr LR, Rosamond WD, Chang PP, Folsom AR, Chambless LE. Heart failure incidence and survival (from the Atherosclerosis Risk in Communities study). Am J Cardiol. 2008;101(7):1016
- Doughty R.N., The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: an individual patient data meta-analysis, European Heart Journal (2012);33(14):1750-1757
- Clinicaltrials.gov, NCT01035255 last accessed online 19 March 2014
- Novartis press release 'PARADIGM-HF trial of Novartis' LCZ696 for chronic heart failure stopped early based on strength of interim results' issued on March 31, 2014
- Mosterd A, Hoes, A, Clinical epidemiology of heart failure, Heart 2007;93:1137
- Cook C, Cole G, Asaria P, Jabbour R, Francis DP. The annual global economic burden of heart failure. Int J Cardiol. 2014.;171(3):368-76
- Neumann T, Biermann J, Erbel R, Neumann A, Wasem J, Ertl G, et al.,. Heart failure: the commonest reason for hospital admission in Germany: medical and economic perspectives. Dtsch Arztebl Int. 2009;106:269-75.
- Stewart S, Jenkins A, Buchan S, McGuire A, Capewell S, McMurray JJ. The current cost of heart failure to the National Health Service in the UK. Eur J Heart Fail. 2002 Jun;4(3):36-71.
- Blais C, et al. Assessing the burden of hospitalized and community-care heart failure in Canada. Can J Cardiol. 2014 Mar; 30(3):352-8 for 3.5% prevalence rate in population 40+ (p.356) in five major provinces of Canada and applying that rate to Canadian population 40+ (17.687 million) from Statistics Canada, Population by sex and age group, 2013, accessed at: http://www.statcan.gc.ca/tables-tableaux/sum-som/l01/cst01/demo10a-eng.htm
- Canadian Heart Failure Network, Rationale for HF Clinics - The Problem: HF, accessed at: http://www.chfn.ca/clinic-resource-manual/rationale-for-hf-clinics citing Brophy JM. Epidemiology of congestive heart failure: Canadian data from 1970 to 1989. Can J Cardiol 1992;8:495-498.
- Canadian Institute for Health Information (CIHI), A Snapshot of Health in Canada as Demonstrated by Top 10 Lists, 2011, p. 10, accessed at: https://secure.cihi.ca/free_products/Top10ReportEN-Web.pdf
- Cook C. et al., The Annual Global Economic Burden of Heart Failure, International Journal of Cardiology (2014), Table 1.
- Canadian Cancer Society's Advisory Committee on Cancer Statistics. Canadian Cancer Statistics 2014, p. 45, Toronto: Canadian Cancer Society; 2014, at: http://www.cancer.ca/en/cancer-information/cancer-101/canadian-cancer-statistics-publication/?region=qc
SOURCE Novartis Pharmaceuticals Canada Inc.
The web app is agile. The REST API is agile. The testing and planning are agile. But alas, data infrastructures certainly are not. Once an application matures, changing the shape or indexing scheme of data often forces at best a top down planning exercise and at worst includes schema changes that force downtime. The time has come for a new approach that fundamentally advances the agility of distributed data infrastructures. Come learn about a new solution to the problems faced by software organ...
Oct. 8, 2015 01:00 PM EDT Reads: 768
Any Ops team trying to support a company in today’s cloud-connected world knows that a new way of thinking is required – one just as dramatic than the shift from Ops to DevOps. The diversity of modern operations requires teams to focus their impact on breadth vs. depth. In his session at DevOps Summit, Adam Serediuk, Director of Operations at xMatters, Inc., will discuss the strategic requirements of evolving from Ops to DevOps, and why modern Operations has begun leveraging the “NoOps” approa...
Oct. 8, 2015 01:00 PM EDT
NHK, Japan Broadcasting, will feature the upcoming @ThingsExpo Silicon Valley in a special 'Internet of Things' and smart technology documentary that will be filmed on the expo floor between November 3 to 5, 2015, in Santa Clara. NHK is the sole public TV network in Japan equivalent to the BBC in the UK and the largest in Asia with many award-winning science and technology programs. Japanese TV is producing a documentary about IoT and Smart technology and will be covering @ThingsExpo Silicon Val...
Oct. 8, 2015 01:00 PM EDT Reads: 250
Organizations already struggle with the simple collection of data resulting from the proliferation of IoT, lacking the right infrastructure to manage it. They can't only rely on the cloud to collect and utilize this data because many applications still require dedicated infrastructure for security, redundancy, performance, etc. In his session at 17th Cloud Expo, Emil Sayegh, CEO of Codero Hosting, will discuss how in order to resolve the inherent issues, companies need to combine dedicated a...
Oct. 8, 2015 01:00 PM EDT Reads: 468
SYS-CON Events announced today that ProfitBricks, the provider of painless cloud infrastructure, will exhibit at SYS-CON's 17th International Cloud Expo®, which will take place on November 3–5, 2015, at the Santa Clara Convention Center in Santa Clara, CA. ProfitBricks is the IaaS provider that offers a painless cloud experience for all IT users, with no learning curve. ProfitBricks boasts flexible cloud servers and networking, an integrated Data Center Designer tool for visual control over the...
Oct. 8, 2015 01:00 PM EDT Reads: 755
In their session at DevOps Summit, Asaf Yigal, co-founder and the VP of Product at Logz.io, and Tomer Levy, co-founder and CEO of Logz.io, will explore the entire process that they have undergone – through research, benchmarking, implementation, optimization, and customer success – in developing a processing engine that can handle petabytes of data. They will also discuss the requirements of such an engine in terms of scalability, resilience, security, and availability along with how the archi...
Oct. 8, 2015 01:00 PM EDT Reads: 355
The Internet of Things (IoT) is growing rapidly by extending current technologies, products and networks. By 2020, Cisco estimates there will be 50 billion connected devices. Gartner has forecast revenues of over $300 billion, just to IoT suppliers. Now is the time to figure out how you’ll make money – not just create innovative products. With hundreds of new products and companies jumping into the IoT fray every month, there’s no shortage of innovation. Despite this, McKinsey/VisionMobile data...
Oct. 8, 2015 12:45 PM EDT
DevOps has often been described in terms of CAMS: Culture, Automation, Measuring, Sharing. While we’ve seen a lot of focus on the “A” and even on the “M”, there are very few examples of why the “C" is equally important in the DevOps equation. In her session at @DevOps Summit, Lori MacVittie, of F5 Networks, will explore HTTP/1 and HTTP/2 along with Microservices to illustrate why a collaborative culture between Dev, Ops, and the Network is critical to ensuring success.
Oct. 8, 2015 12:45 PM EDT
Apps and devices shouldn't stop working when there's limited or no network connectivity. Learn how to bring data stored in a cloud database to the edge of the network (and back again) whenever an Internet connection is available. In his session at 17th Cloud Expo, Bradley Holt, Developer Advocate at IBM Cloud Data Services, will demonstrate techniques for replicating cloud databases with devices in order to build offline-first mobile or Internet of Things (IoT) apps that can provide a better, ...
Oct. 8, 2015 12:45 PM EDT Reads: 503
IT data is typically silo'd by the various tools in place. Unifying all the log, metric and event data in one analytics platform stops finger pointing and provides the end-to-end correlation. Logs, metrics and custom event data can be joined to tell the holistic story of your software and operations. For example, users can correlate code deploys to system performance to application error codes.
Oct. 8, 2015 12:45 PM EDT Reads: 163
Containers are revolutionizing the way we deploy and maintain our infrastructures, but monitoring and troubleshooting in a containerized environment can still be painful and impractical. Understanding even basic resource usage is difficult - let alone tracking network connections or malicious activity. In his session at DevOps Summit, Gianluca Borello, Sr. Software Engineer at Sysdig, will cover the current state of the art for container monitoring and visibility, including pros / cons and li...
Oct. 8, 2015 12:30 PM EDT Reads: 139
As-a-service models offer huge opportunities, but also complicate security. It may seem that the easiest way to migrate to a new architectural model is to let others, experts in their field, do the work. This has given rise to many as-a-service models throughout the industry and across the entire technology stack, from software to infrastructure. While this has unlocked huge opportunities to accelerate the deployment of new capabilities or increase economic efficiencies within an organization, i...
Oct. 8, 2015 12:15 PM EDT Reads: 211
WebRTC is about the data channel as much as about video and audio conferencing. However, basically all commercial WebRTC applications have been built with a focus on audio and video. The handling of “data” has been limited to text chat and file download – all other data sharing seems to end with screensharing. What is holding back a more intensive use of peer-to-peer data? In her session at @ThingsExpo, Dr Silvia Pfeiffer, WebRTC Applications Team Lead at National ICT Australia, will look at di...
Oct. 8, 2015 12:00 PM EDT Reads: 597
For almost two decades, businesses have discovered great opportunities to engage with customers and even expand revenue through digital systems, including web and mobile applications. Yet, even now, the conversation between the business and the technologists that deliver these systems is strained, in large part due to misaligned objectives. In his session at DevOps Summit, James Urquhart, Senior Vice President of Performance Analytics at SOASTA, Inc., will discuss how measuring user outcomes –...
Oct. 8, 2015 12:00 PM EDT Reads: 429