Inclisiran is the first of a new type of cholesterol-lowering treatment which uses RNA interference (RNAi) to boost the liver’s ability to remove LDL-cholesterol from the blood.
NICE's decision to back inclisiran for NHS use follows an agreement between NHS England and NHS Improvement and Novartis, which will make the drug available at a discount to its list price.
Inclisiran is given by subcutaneous injection, either on its own or alongside statins or other cholesterol-lowering drugs. Patients receive a second dose three months after an initial dose, and then two more doses each year.
NHS England said a deal with the drug's manufacturer Novartis would allow 300,000 people to receive it over the next three years - suggesting GP practices could be expected to deliver two inclisiran jabs to 100,000 patients a year. Administering the drug in GP surgeries would spare patients regular hospital visits, it added.
Officials estimate that inclisiran could 'prevent 55,000 heart attacks and strokes, saving 30,000 lives within the next decade'.
Clinical trial evidence shows that inclisiran may help lower cholesterol levels when other treatments have not reduced them enough. However, there is no data directly comparing inclisiran with the other treatments ezetimibe, alirocumab or evolocumab. There is also no long term evidence yet on inclisiran’s effect on cardiovascular outcomes.
In people who have never had a cardiovascular event, the cost-effectiveness estimates were 'very uncertain' and deemed likely to be above what NICE considers an acceptable use of NHS resources.
Meindert Boysen, NICE deputy chief executive and director of the Centre for Health Technology Evaluation, said: 'Inclisiran represents a potential game-changer in preventing thousands of people from dying prematurely from heart attacks and strokes.
'We’re therefore pleased to be able to recommend it as a cost-effective option on the NHS supported by the ground-breaking deal between NHS England and NHS Improvement and Novartis - a deal that could see as many as 300,000 people with high cholesterol or mixed dyslipidaemia who have already had a previous cardiovascular event receive the drug over the next 3 years.'
When taken up by liver cells, inclisiran suppresses the translation of proprotein convertase subtilisin kexin type 9 — the same enzyme targeted by alirocumab and evolocumab. This results in increased LDL-C receptor recycling and expression, increasing LDL-C uptake and lowering circulating LDL-C.
The efficacy of inclisiran was evaluated in three phase III studies in 3660 patients with atherosclerotic cardiovascular disease (coronary heart disease, cerebrovascular disease or peripheral artery disease), atherosclerotic cardiovascular disease risk equivalents (type II diabetes, familial hypercholesterolaemia, or a 10-year risk of having a cardiovascular event of ≥20%) and/or familial hypercholesterolaemia.
Patients were taking a maximally tolerated dose of statin with or without other lipid-modifying therapy and required additional LDL-C reduction; approximately 17% of patients were statin-intolerant.
In a pooled analysis, the placebo-corrected change in LDL-C with inclisiran at day 510 was −50.7% (95% CI −52.9% to −48.4%; p<0.0001) and the corresponding time-adjusted change in LDL-C was −50.5% (95% CI −52.1% to −48.9%; p<0.0001).
The only adverse events associated with inclisiran were reactions at the injection site (8.2%).