High cholesterols halved by twice yearly injections of a unique drug
NICE provisionally recommended in September 2021 that an RNA-based drug, Inclisiran, be used by the NHS for those people with a high cholesterol or an abnormal lipid profile (LDL >2.6 mmol/L) who have already had a heart attack or stroke. The novel anti-cholesterol drug is given twice a year by injection. Clinical trials have shown that it can lower LDL cholesterol by about 50%. This type of medication, siRNA, is fairly novel with the first molecule of its class first licenced in 2018 and none in wide usage.
How does Inclisiran work? Fats including cholesterol are insoluble in water and are therefore carried in the blood stream inside a parcel, called a lipoprotein particle; LDL particles are rich in cholesterol. Receptors on the surface of liver and other body cells remove and destroy cholesterol-carrying lipoprotein particles from the circulation. Normally, a protein called PCSK9, produced by the liver, binds to lipoprotein receptors and regulates receptor turnover by promoting their breakdown. The new drug Inclisiran is a small two-stranded RNA molecule. It interferes genetically with the liver production of PCSK9 so that receptor turnover is reduced and there are more receptors on cell surfaces to remove LDL lipoprotein particles. PCSK9 antibody drugs work by the removing the protein from the circulation and are already in widespread use, reducing LDL-cholesterol by 60% (however LDL criteria are higher and the drug is delivered by injection every 2 weeks).
Inclisiran is expensive, but NICE considered it cost-effective in people who have previously had a cardiovascular event and whose cholesterol levels remain high on maximum tolerated lipid lowering therapy. The drug’s cost-effectiveness for those with high lipids who have not had a cardiovascular event will be judged when current clinical trials have reported its ability to prevent them.
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.”
The final announcement is due on 6th October 2021 after a period of feedback for the current proposal. After that local formulary primary care committees will have to meet in order to determine how best to provide the service, as it will require people to identify patients and administer the medication, so it may take a little while longer to become widely available.