Novartis’ heart failure medicine Entresto™ (sacubitril/valsartan) receives EC authorisation
EC grants marketing authorisation to Entresto™
- Entresto (sacubitril/valsartan) is the first and only treatment to show a significant mortality benefit in a head-to-head trial against ACE-inhibitor enalapril1
- At the end of the study, sacubitril/valsartan was superior to enalapril in reducing the risks of mortality and of hospitalisation for heart failure
- Heart failure is a life-threatening condition with around 550,000 people diagnosed in the UK and many more thought to be affected 
Frimley, UK, November 24 2015 – Novartis announced today that the European Commission (EC) has granted marketing authorisation to Entresto™ (sacubitril/valsartan) for the treatment of adult patients with symptomatic chronic heart failure with reduced ejection fraction (HFrEF). Sacubitril/valsartan is a twice-a-day tablet and has a unique mode of action, which is thought to reduce the strain on the failing heart3.
The authorisation is based on results from the 8,442-patient PARADIGM-HF study in patients with HFrEF, which was stopped early when it was shown sacubitril/valsartan significantly reduced the risk of cardiovascular death versus ACE-inhibitor enalapril1. At the end of the study, sacubitril/valsartan was superior to enalapril in reducing the risks of mortality and of hospitalisation for heart failure. Analysis of safety data showed that sacubitril/valsartan had a similar tolerability profile to enalapril1.
“Heart failure is a potentially life-threatening condition that has a major impact on patients and their carers,” said Dimitrios Georgiopoulos MD, Chief Scientific Officer, Novartis Pharmaceuticals UK Ltd. He added, “There is a real need for new and effective treatments that reduce mortality and morbidity while improving patients’ quality of life. Sacubitril/valsartan is a new first-in-class treatment option for heart failure patients with reduced ejection fraction that demonstrated a significant mortality benefit, including reducing the risk of sudden death versus, the current standard of care.”
Novartis is currently preparing for sacubitril/valsartan to be available in the UK before the end of 2015. Since September 2015, sacubitril/valsartan has been available to patients under the Early Access to Medicines Scheme (EAMS). Patients who are currently receiving sacubitril/valsartan under EAMS will continue to do so until the Health Technology Assessment completes its appraisal of the medicine, anticipated in 2016. No new patients, however, will be able to receive sacubitril/valsartan under EAMS now that it has received European marketing authorisation. Novartis is working with NICE and the Scottish Medicines Consortium (SMC) to ensure as many eligible patients as possible will be able to benefit from sacubitril/valsartan once it has been appraised.
Heart failure is a highly debilitating, life-threatening condition, which affects around 550,000 people in the UK2, costing the NHS about £2.3bn a year , . Heart failure has a poor prognosis: around 61% of patients diagnosed with heart failure die within five years7 and survival rates are worse than certain cancers, such as breast and prostate.
Despite the prevalence, most people fail to recognise the symptoms, meaning many are misdiagnosed or incorrectly attribute the signs to growing older.
Sacubitril/valsartan exhibits the mechanism of action of an angiotensin receptor neprilysin inhibitor (ARNI) that reduces the strain on the failing heart. A twice-a-day tablet, it acts to enhance the protective neurohormonal systems of the heart (natriuretic peptide system system) while simultaneously suppressing the harmful system (the renin-angiotensin-aldosterone system (RAAS)3.
Results from the 8,442 patient PARADIGM-HF comparing sacubitril/valsartan to enalapril showed:
Overall 20% reduced risk on primary end point of cardiovascular death or first hospitalisation for heart failure vs enalapril (sacubitril/valsartan – 914 (21.8%) vs enalapril – 1117 (26.5%). ARR: 4.7%)1
20% (p=0.00004) reduced risk of cardiovascular death vs enalapril (4187 (13.3%) vs 4212 (16.5%). ARR: 3.2%)1,8
21% (p=0.00004) reduced risk of first hospitalisation for heart failure vs enalapril
(4187 (12.8%) vs 4212 (15.6%). ARR: 2.8%)1,8
16% (p=0.0005) reduced risk of all-cause mortality vs enalapril (711 (17%) vs 835 (19.8%). ARR: 2.8%)21,8
20% (p=0.008) reduced risk of sudden death vs enalapril (250 (6%) vs 311 (7.4%). ARR: 1.4%)9
Patients’ reports of how well they felt and doctor’s assessments of disease severity were also significantly better with sacubitril/valsartan than enalapril10
Fewer patients on sacubitril/valsartan discontinued study medication for any adverse event compared to those on enalapril. The sacubitril/valsartan group had more hypotension and non-serious angioedema but less renal impairment, hyperkalemia and cough than the enalapril group1.
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, eye care and cost-saving generic pharmaceuticals. Novartis is the only global company with leading positions in these areas. In 2014, the Group achieved net sales of USD 58.0 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 120,000 full-time-equivalent associates. Novartis products are available in more than 180 countries around the world. For more information, please visit www.novartis.co.uk
1. McMurray JJV et al. Angiotensin-Neprilysin Inhibition versus Enalapril in Heart Failure, N Engl J Med 2014
2. British Heart Foundation. Treating heart failure patients in the community with intravenous diuretics. Available at: https://www.bhf.org.uk/~/media/files/publications/healthcare-and-innovations/iv-diuretics-in-the-community_sirivd1.pdf Last accessed November 2015
3. ENTRESTO Summary of Product Characteristics
4. MHRA Decision: Early Access to Medicines Scheme (EAMS) scientific opinion: sacubitril/valsartan.
Available at: https://www.gov.uk/government/publications/early-access-to-medicines-scheme-eams- 5. NHS England, 2015. About the National Health Service (NHS). Available at:
https://www.nhs.uk/NHSEngland/thenhs/about/Pages/overview.aspx Last accessed November 2015
6. NICE, 2010. Costing report for NICE Clinical Guideline 108, Chronic Heart Failure. Available at:
https://www.nice.org.uk/guidance/cg108/resources/costing-report-134800813 Last accessed November 2015
7. Sutherland K. Bridging the quality gap: heart failure. 2010. London. Health Foundation. Available at:
https://www.health.org.uk/sites/default/files/BridgingTheQualityGapHeartFailure_0.pdf Last accessed November 2015
8. Novartis Pharmaceuticals Data on File [LCZ15-C025-270] Last accessed November 2015
Date of preparation: November 2015. ENT15-E009 3/3
9. Desai AS, et al. Effect of the angiotensin-receptor-neprilysin inhibitor LCZ696 compared with enalapril on mode of death in heart failure patients. Eur Heart J. 2015 Aug 7;36(30):1990-7
10. Packer M, et al. Angiotensin-Neprilysin Inhibition and Clinical Progression in Surviving Patients with Heart Failure. Circulation. 2015;131:54-61