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NICE sets out draft recommendations for evolocumab in Final Appraisal Determination

NICE has published a recommendation that supports the use of evolocumab (brand name Repatha), alone or in combination with other cholesterol-lowering therapies, for several types of patients at particularly high risk of cardiovascular events with persistently high cholesterol.1

The NICE recommendation is based on a positive assessment of evolocumab’s clinical and cost effectiveness.

Evolocumab is a human monoclonal antibody that blocks a protein called PCSK9 – which inhibits the body’s natural system for eliminating ‘bad cholesterol’ (low-density lipoprotein cholesterol, LDL-C) from the blood. It was the first in this new class of cholesterol-lowering medicines to gain marketing authorisation in Europe.

The new draft guidance recommends evolocumab for patients whose LDL-C persists above levels specified by NICE despite maximal tolerated lipid-lowering therapy. NICE specifies an LDL-C level above 3.5mmol/l where the patient has existing cardiovascular disease alongside heterozygous familial hypercholesterolaemia (HeFH) or a very high risk of further cardiovascular events without HeFH.

It specifies an LDL-C level above 4.0mmol/l for treatment of patients with cardiovascular disease who have a high risk (without HeFH); and an LDL-C level above 5.0mmol/l for patients with HeFH who do not have cardiovascular disease.1

Dr Derek Connolly, Consultant Interventional Cardiologist at Birmingham City Hospital, said: “Cardiovascular disease remains one of our biggest killers. Persistent high cholesterol has been shown to increase the risk of atherosclerosis, heart attacks and strokes. This is especially true in patients whose family genetics are driving their cholesterol to high levels (so-called FH or familial hypercholesterolaemia). However any patient with evidence of existing cardiovascular disease may benefit from cholesterol reduction. By lowering cholesterol in such patients there is real potential to avoid death and disability from heart attacks and strokes – events which are very costly in both personal and financial terms. So today’s news from NICE is excellent for patients and excellent for the NHS.”

The science behind evolocumab is based on genetic insights into people who have especially high,2 and especially low,3 levels of PCSK9. Clinical trials have shown that a fortnightly injection of 140mg evolocumab on top of statin treatment reduced LDL-C by between 55 and 75% compared with statins alone.4

FH is one of the most common life-threatening genetic diseases,5 affecting between 1 in 500 and 1 in 200 people (0.2–0.5%).5–7 A national audit of FH patients found that – even among patients attending specialist lipid clinics – only 44% of adult patients achieved the recommended NICE target of 50% reduction in LDL-C from the untreated level.8

A study recently published in the Journal of the American Medical Association evaluated evolocumab as a cholesterol-lowering agent for people who are unable to take statins.9 NICE has defined statin intolerance as ‘the presence of clinically significant adverse effects that represent an unacceptable risk to the patient or that may reduce compliance with therapy’.10

“We are very encouraged by the positive draft recommendations of NICE to date,” said Tony Patrikios, Executive Medical Director, Amgen UK and Ireland. “There is a clear clinical need for new medicines that can lower LDL-C in patients who have persistently high cholesterol despite statin therapy, and who are living with a high risk of future cardiovascular disease.”

“In Repatha, Amgen has applied almost four decades of experience in developing and manufacturing biologic medicines to deliver this new advance for patients in the UK and their NHS healthcare professionals. We are a partner with them in the mission to tackle the burden of cardiovascular disease in this country – a mission that has been significantly progressed with today’s news from NICE.”

The effect of evolocumab on cardiovascular morbidity and mortality has not yet been determined.4  Evidence has shown that high cholesterol increases the risk of atherosclerosis, heart attack and stroke.11 An ongoing study, FOURIER, is exploring the extent to which the LDL-C reductions achieved by evolocumab treatment may prevent future cardiovascular events such as heart attacks and strokes. From a total of 27,564 patients enrolled globally in the trial there are 1490 in the UK; spread across 74 trial centres nationwide.

The NICE FAD for evolocumab published today is not NICE’s Final Guidance on evolocumab – it is expected to become Final Guidance to the NHS in England and Wales in June 2016, and then the NHS will have 90 days to ensure it is implemented across the health system.


  1. National Institute for Health and Care Excellence. Final appraisal determination – Evolocumab for treating primary hypercholesterolaemia and mixed dyslipidaemia. 2016. Online here.
  2. Abifadel M, Varret M, Rabès J-P et al. Nature Genetics 2003.34;2.
  3. Cohen JC, Boerwinkle E, Mosley TH et al. N Engl J Med 2006; 354:1264-1272
  4. Repatha® (evolocumab) Summary of Product Characteristics. Online Here.
  5. Goldberg AC, Hopkins PN, Toth PP et al. J Clin Lipid. 2011;5:S1-S8.
  6. NICE Clinical Guideline 71. Identification and management of familial hypercholesterolaemia. August 2008. Online Here.
  7. Nordestgaard BG, Chapman MJ, Humphries SE et al. Eur Heart J. 2013;34:3478-90.
  8. Pedersen KMV et al. National Clinical Audit of the Management of Familial Hypercholesterolaemia 2010: Full Report. Clinical Standards Department, Royal College of Physicians, December 2010.
  9. Nissen SE, Stroes E, Dent-Acosta RE et al for the GAUSS-3 Investigators. Efficacy and Tolerability of Evolocumab vs Ezetimibe in Patients With Muscle-Related Statin Intolerance: The GAUSS-3 Randomized Clinical Trial. JAMA. Published online April 03, 2016.
  10. NICE Key Therapeutic Topic (KTT3). Lipid-modifying drugs. January 2015. Online Here.
  11. NHS Choices – High Cholesterol. Online Here.

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