September 1, 2021

expert reaction to the approval by NICE of the anti-cholesterol drug inclisiran

The National Institute for Health and Care Excellence (NICE) has today issued a draft final guidance recommending the novel anti-cholesterol drug inclisiran for use in people with high cholesterol who have already had a previous cardiovascular event, to reduce the chances of them having another.

Prof Sir Mark Caulfield, Professor of Clinical Pharmacology, Queen Mary University of London (QMUL), said:

“Cholesterol-lowering is a vital part of cardiovascular disease prevention. This NICE guidance sets out the role of inclisaran in prevention of further future cardiovascular events. This clarifies the use and evidence needed for the use of this RNA based therapy in the context of other cholesterol-lowering therapies that are already in use in the NHS. It helpfully expands the options for patients.”

Professor Sir Nilesh Samani, Medical Director, British Heart Foundation (BHF), said:

“The approval of inclisiran is good news for heart patients in the UK. The twice-yearly injection to lower LDL or ‘bad’ cholesterol in patients with existing heart disease, whose cholesterol is not adequately controlled with statins or other drugs, will help to prevent people from having further heart attacks or strokes, ultimately maximising the numbers of lives saved.

“Inclisiran is particularly attractive because it only needs to be given twice a year by a simple injection under the skin. More research is needed to confirm the full extent of its benefits, but I anticipate that in the future it will also be approved to lower cholesterol for a much wider group of people to prevent them from having a heart attack or stroke in the first place.”

Prof Kausik Ray, Professor of Public Health and Director of the Imperial Centre for Cardiovascular Disease Prevention, Imperial College London, said:

“This is a game changer for patients and the NHS.

“This is the first and only small interfering RNA (siRNA) based therapy for cholesterol lowering. We know that despite the use of statins, patients with established cardiovascular disease have an average LDL cholesterol (LDL-C) of about 2.6 mmol/L, and a 10-year residual risk of cardiovascular events of 29%. In order to achieve lower cholesterol levels, combination therapies are needed in addition to statins.

“Statins and inclisiran are complimentary – statins make more cholesterol receptors, and inclisiran, by stopping the production of a protein called PCSK9, makes these receptors last or survive longer. This means the two treatments reduce LDL-C by about 75-80% when compared to no treatment. Twice-a-year dosing will safely provide an average annualised reduction in population level LDL-C of approximately 50%. Lowering population level LDL-C from 2.6 to about 1.3 would reduce cardiovascular events by about 30%, and bring 10-year risk down from 29% to around 20%.

Is this good news for patients?

“It’s great news for patients. It will reduce their medication burden and offer convenience.

Which patients are likely to benefit?

“It’s good for anyone who is at high risk of cardiovascular disease and in need of further LDL-C lowering. NICE have approved it for those with established cardiovascular disease. The obvious disappointment is that they don’t seem to have thought it cost effective for familial hypercholesterolaemia (FH), where patients have genetically elevated LDL-C and limitations on treatments available. This needs further thought.

Does this replace the need for other cholesterol-lowering drugs like statins?

“No. It’s designed to be an add-on, but for those who can’t tolerate statins it can be used on its own.

What are the key advantages and disadvantages of this treatment?

“Convenience is a key advantage. Twice-a-year injections are convenient. Plus, if patients show up to get the injection, you know the drug is in their body and will work until their next injection, so clinicians don’t have to rely on patients taking additional medication or monoclonal antibody treatments (which require self-injection every two weeks).

Do you agree with the NICE statement that this news is a potential game changer and could prevent thousands of people dying prematurely each year?

“Absolutely. Bringing population level LDL-C down from 2.6 to 1.3, which is what the introduction of inclisiran should do, when the risk of a cardiovascular event despite current standard treatment is 29%, means that that risk will be reduced by approximately 9% in absolute terms. So, if 300,000 patients are treated, that’s about 30,000 events averted in a 10-year period.”

‘Final appraisal document – Inclisiran for treating primary hypercholesterolaemia or mixed dyslipidaemia’ by the National Institute for Health and Care Excellence was published at 00:01 UK time on Wednesday 1^st September 2021.

Declared interests

Prof Kausik Ray: “I was lead investigator on the ORION-10 and ORION-11 inclisiran trials.”

None others received.