NICE issues draft guidance on evolocumab for lipid disorder
18 November 2015
NICE has published draft guidance not recommending evolocumab (Repatha, Amgen) as an option for people with high cholesterol (primary hypercholesterolaemia - heterozygous-familial and non-familial) and mixed dyslipidaemia.
People with hypercholesterolaemia and mixed dyslipidaemiai have high concentrations of cholesterol in their blood. In primary non-familial hypercholesterolaemia, a number of genes interact with dietary and other factors such as smoking and lack of exercise to cause high cholesterol levels. Primary non-familial hypercholesterolaemia affects an estimated 1.5 million people in England. Primary heterozygous-familial hypercholesterolaemia is an inherited condition caused by a faulty gene and affects about 106,000 people in England. People with this condition have raised cholesterol levels from birth.
The draft guidance does not recommend evolocumab, alone or in combination with lipid-lowering therapies, for treating primary hypercholesterolaemia or mixed dyslipidaemia in adults for whom lipid-modifying therapies, in line with current NICE guidance, would be considered.
People with hypercholesterolaemia have an increased risk of cardiovascular disease (CVD) because long term raised cholesterol levels accelerate the build-up of fatty deposits in the arteries (atherosclerosis). The narrowing of the arteries can eventually lead to angina, heart attacks and strokes. CVD is a common cause of death in England, accounting for approximately 150,000 deaths in 2012.
Evolocumab is an antibody that targets a specific protein, called PCSK9. PCSK9 reduces the number of receptors on the liver that remove LDL cholesterol (also known as 'bad' cholesterol) from the blood. By blocking PCSK9's ability to work, more receptors are available to get rid of LDL cholesterol from the blood and, as a result, lower LDL cholesterol levels.
Meindert Boysen, Programme Director at NICE, said: "The Committee concluded that although evolocumab was effective in reducing levels of LDL cholesterol in people with primary hypercholesterolaemia, there have been no clinical trials to measure the direct effect of evolocumab on CVD events. They felt the question of whether reducing LDL cholesterol with evolocumab would reduce angina, heart attacks and strokes remains unanswered.
"The Committee also considered that the analyses presented by the company had several limitations which called in to question the reliability of the cost-effectiveness results. Importantly, the Committee was concerned that the company had estimated the risks of CVD by using the Framingham risk equations, which have been shown to overestimate CVD risk in a UK population, instead of the NICE-recommended and UK-validated QRISK2 assessment tool. The Committee was also concerned that the company had used an unrealistically high factor to adjust the risk of CVD in people with heterozygous-familial hypercholesterolaemia.
"The Committee concluded that the degree of uncertainty in the cost-effectiveness evidence was too high for it to be able to make well-founded recommendations about evolocumab."
Consultees, including the company, healthcare professionals and members of the public have until 8 December 2015 to comment on the preliminary guidance. Comments received during this consultation will be fully considered by the Committee at its meeting on 13 January 2016 and following this meeting the next draft guidance will be issued.
Until final guidance is issued, NHS bodies should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance on a technology, it replaces local recommendations across the country.
For more information call the NICE press office on 0300 323 0142 or out of hours on 07775 583 813.
Notes to Editors
I Mixed dyslipidaemia is defined as elevations in LDL cholesterol and triglyceride levels that are often accompanied by low levels of high-density lipoprotein (HDL) cholesterol.
About the draft guidance
The draft guidance on will be available on the NICE website at http://www.nice.org.uk/guidance/indevelopment/gid-tag498 from 18 November.
Evolocumab (Repatha, Amgen) is a monoclonal antibody which inhibits an enzyme proprotein convertase subtilisin/kexin type 9 (PCSK9) involved in down-regulation of low-density lipoprotein receptors. Evolocumab therefore increases receptor density and lowers LDL- cholesterol. It is administered by subcutaneous injection.
Evolocumab has a marketing authorisation in the UK for treating 'adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet:
in combination with a statin or statin with other lipid lowering therapies in patients unable to reach LDL‑C goals with the maximum tolerated dose of a statin or,
alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated.'
Evolocumab costs £170.10 for a 140‑mg prefilled pen or syringe (excluding VAT; MIMS, September–November 2015). The annual cost of treatment per patient is about £4448.60 for 140mg every 2 weeks, and £6123.60 for 420 mg monthly.
The company has agreed a patient access scheme with the Department of Health. If evolocumab had been recommended, this scheme would provide a simple discount to the list price of evolocumab with the discount applied at the point of purchase or invoice. The level of the discount is commercial in confidence.
The Committee noted the following base-case incremental cost-effectiveness ratios (ICERs) estimated by the company:
Non-familial hypercholesterolaemia without CVD: £74,300 per quality-adjusted life year (QALY) gained for evolocumab plus statin compared with ezetimibe plus statin (statin-tolerant), and £78,800 per QALY gained for evolocumab compared with ezetimibe (statin-intolerant).
Non-familial hypercholesterolaemia with CVD: £46,000–50,900 per QALY gained for evolocumab plus statin with or without ezetimibe compared with ezetimibe plus statin (statin-tolerant), and from £49,300–52,800 per QALY gained for evolocumab with or without ezetimibe compared with ezetimibe (statin-intolerant).
Heterozygous-familial hypercholesterolaemia: £22,900–24,800 per QALY gained for evolocumab plus statin with or without ezetimibe compared with ezetimibe plus statin (statin-tolerant), and £23,900–25,600 per QALY gained for evolocumab with or without ezetimibe compared with ezetimibe (statin-intolerant).
The Committee agreed that the analyses presented by the company had several limitations, which made it unsure about the reliability of the ICERs, some of which were already above the maximum acceptable ICERs normally considered to represent a cost-effective use of NHS resources (£20,000–30,000 per QALY gained), and could be substantially higher when the limitations are addressed. The Committee considered that the degree of uncertainty in the cost-effectiveness evidence was too high for it to be able to make recommendations about evolocumab. It therefore concluded not to recommend evolocumab for primary hypercholesterolaemia (heterozygous-familial and non-familial) or mixed dyslipidaemia in adults.
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