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The draft guidance does not recommend alirocumab, alone or in combination with lipid-lowering therapies, for treating primary hypercholesterolaemia or mixed dyslipidaemia in adults for whom lipid-modifying therapies have not lowered cholesterol levels enough.

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.

Alirocumab 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.

Professor Carole Longson MBE, Director of the NICE Centre for Health Technology Evaluation, said: “The committee concluded that alirocumab is clinically effective in reducing LDL-c levels when compared with placebo, ezetimibe or statins in people with hypercholesterolaemia. However, it was concerned that alirocumab had not been compared with the combination therapy of ezetimibe plus a statin, in the large population of people with non-familial hypercholesterolaemia.

“The committee also noted that the trials were not able to provide robust information on important cardiovascular outcomes. They concluded that, although it was reasonable to infer that alirocumab would reduce cardiovascular events, the extent of this reduction was uncertain.

“The committee further recognised that most of the value for money analyses resulted in ICERs exceeded the range normally considered to be a cost-effective use of NHS resources (up to £20,000–30,000 per QALY gained).

“In view of these concerns, the committee concluded that alirocumab could not be considered a cost effective use of NHS resources for people with hypercholesterolaemia.”

Consultees, including the company, healthcare professionals and members of the public have until 29 February 2016 to comment on the preliminary guidance. Comments received during this consultation will be fully considered by the Committee at its meeting on 9 March 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.

Ends

For more information call the NICE press office on 0300 323 0142/ pressoffice@nice.org.uk or out of hours on 07775 583 813.

Notes to Editors

References

^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

1. The draft guidance will be available on the NICE website at http://www.nice.org.uk/guidance/indevelopment/gid-tag512 from 8 February.
2. Alirocumab 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 modification therapies (LMTs) in patients unable to reach LDL-c goals with the maximal tolerated dose of statin (when used as recommended by treatment guidelines) or,
  alone or in combination with other LMTs in patients who are statin intolerant or                  for whom a statin is contraindicated.’

Alirocumab is given by subcutaneous injection. The recommended dose is either 75 mg or 150 mg every 2 weeks.

1. Alirocumab costs £168 for a 75 mg or 150 mg single-use prefilled pen (excluding VAT, company’s submission).
2. The Committee noted the following base-case incremental cost-effectiveness ratios (ICERs) estimated by the company:

• For the primary prevention heterozygous familial hypercholesterolaemia population:

-      £67,200 per QALY gained for alirocumab and a statin plus ezetimibe compared with a statin and ezetimibe

-      £45,800 per QALY gained for alirocumab and ezetimibe compared with ezetimibe alone in people who are unable to take statins.

• For the secondary prevention heterozygous familial hypercholesterolaemia population:

-      £33,300 per QALY gained for alirocumab and a statin plus ezetimibe compared with a statin and ezetimibe

-      £22,000 per QALY gained for alirocumab and ezetimibe compared with ezetimibe alone for people who are unable to take statins.

• For the high-risk cardiovascular (non-familial hypercholesterolaemia) population:

-      £42,100 per QALY gained for alirocumab and a statin compared with a statin alone

-      £34,600 per QALY gained for alirocumab and ezetimibe compared with ezetimibe alone for people who are unable to take statins.

• For the recurrent events/polyvascular disease (non-familial hypercholesterolaemia) population:

-      £44,759 per QALY gained for alirocumab and a statin compared with a statin alone.

-     £33,519 per QALY gained for alirocumab and ezetimibe compared with ezetimibe alone for people who are unable to take statins.