A new drug called inclisiran has just been approved by the National Institute for Health and Care Excellence (NICE) and could potentially be a ‘game changer’ for people who have previously had a heart attack or stroke. NICE (2021) issued guidance on the 1 September 2021 that recommended the new anti-cholesterol drug inclisiran (Leqvio, Novartis) for people with primary hypercholesterolaemia or mixed dyslipidaemia, who have already had a cardiovascular event, such as a myocardial infarction or stroke.
The decision follows an agreement on a commercial deal privately agreed between the drug company Novartis, NHS England and NHS Improvement. The deal is particularly striking, as inclisiran will be available at a discount to its list price, for an undisclosed amount. The drug comes as an injection and would only need to be administered twice a year. Those with hypercholesterolaemia who have had a previous cardiac event would also be eligible for this new drug, with the aim of preventing them from having another cardiac event. Inclisiran can be used on its own or alongside statins or other cholesterol-lowering drugs.
Inclisiran is the first of its kind of a cholesterol-lowering treatment, with pharmacokinetics that differ from traditional methods of treatment. It uses RNA interference (RNAi) to boost the liver's ability to remove harmful cholesterol from the bloodstream (NICE, 2021).
Patients with primary hypercholesterolaemia and those who have dyslipidaemia are known to be at a higher risk of cardiovascular events. The way the current system in the UK works is to encourage the patient to undertake dietary changes and medicate with statins and other medications that help to lower cholesterol, either alone or in combination. The trial evidence has revealed that this new treatment may help to reduce cholesterol when these other methods have been unable to, demonstrating its potential efficacy in a situation where such an alternative mode of action would be beneficial, and possibly even lifesaving.
However, there are no data to directly compare inclisiran with other treatments, such as ezetimibe, alirocumab or evolocumab, and there is no long-term evidence as yet that shows inclisiran's long-term efficacy on cardiovascular outcomes (NICE, 2021). However, inclisiran is considered by NICE (2021) as cost effective for people who have previously had a cardiovascular event and whose cholesterol levels remain high even after using the maximum-tolerated lipid-lowering therapy.
The cost-effectiveness estimates remained uncertain for those who have never actually had a cardiovascular event, but they were thought to likely be above what NICE would deem an acceptable use of NHS resources. A clinical trial is planned that will analyse whether inclisiran can reduce the risk of cardiovascular events in this population (NICE, 2021).
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.’
According to Novartis, the approval is based on the results of the robust ORION clinical development programme, where the researchers found that inclisiran provided an effective and sustained low-density lipoprotein cholesterol (LDL-C) reduction of up to 52% in patients with a raised level of LDL-C, despite having the maximum amount that can be given of statin therapy. Following the first dose, the second dose would be at 3 months, but further doses would then be at 6-month intervals. The idea is that, once treatment has started, long-term adherence can be maintained.
Inclisiran works by providing a sustained and effective reduction in LDL-C for patients specifically with atherosclerotic disease, atherosclerotic cardiovascular disease risk-equivalent patients and those with heterozygous familial hypercholesterolaemia (HeFH) (Novartis, 2021).
However, it is important to exercise caution with this drug, so that society does not become completely dependent on pharmacological approaches alone. Dietary modification, especially where saturated fat is concerned, swapping out red meat for other protein sources, consuming more fibre, engaging in exercise and supporting patients to reduce or quit smoking and drinking and manage their mental health can have a significant impact on cardiovascular health (British Heart Foundation (BHF), 2021).
Some patients may have more complex needs and have dual diagnoses, so, by helping them to manage their mental health and any addictions with referrals for mental health services in NHS trusts, self-referrals to Improving Access to Psychological Therapies (IAPT), and referrals to local authority addiction services, the patient can be supported to manage their physical and mental health, make healthier choices and develop the confidence to exercise more, which may lower their cholesterol as a result.