Inclisiran: UK to roll out new cholesterol lowering drug from next yearBMJ 2020; 368 doi: https://doi.org/10.1136/bmj.m139 (Published 13 January 2020) Cite this as: BMJ 2020;368:m139
The UK government is to launch a major clinical trial of the novel cholesterol lowering drug inclisiran later this year and aims to make it available to NHS patients from 2021.
Inclisiran, an investigational treatment taken by injection twice a year, is a cholesterol lowering therapy in the small interfering RNA (siRNA) class. It has not yet been approved by the US Food and Drug Administration or the European Medicines Agency but is expected to be filed for approval later this year as a preventive add-on treatment to statins for patients who already have a cardiovascular disease diagnosis.
Results of a phase III study of inclisiran involving patients who had elevated LDL cholesterol concentrations despite taking the maximum dose of statins, which was presented at the European Society of Cardiology conference last September, showed that the drug halved LDL cholesterol concentrations at 17 months.1
The government said that the study results suggested that if inclisiran were given to 300 000 patients a year it could help prevent 55 000 heart attacks and strokes and save 30 000 lives over the next 10 years.
The Department of Health and Social Care for England announced a deal with Novartis (the drug’s manufacturer), NHS England, the National Institute for Health Research, and Oxford University to conduct a large UK trial of the drug. And in a move that the government described as a world first, NHS England is expected to agree a population level commercial arrangement with Novartis to make the drug widely available to patients as soon as 2021.
Inclisiran works by interfering with the production of the PCSK9 protein, which blocks the liver’s ability to clear LDL cholesterol from the blood. With less PCSK9 available, the liver is able to process more LDL cholesterol and reduce blood concentrations. Inclisiran works slightly differently from alirocumab and evolocumab, which inactivate PCSK9. These other drugs are given by injection every two weeks.
Martin Landray, professor of medicine and epidemiology at the University of Oxford, where the new study will be conducted, said, “The trial will both provide a very reliable test of the efficacy and safety of inclisiran to support a population health approach to the management of cholesterol and act as an exemplar for future trials of other treatments in the UK.”
The health department said that the National Institute for Health and Care Excellence would assess the drug “at the earliest opportunity.”
Experts emphasised the need to assess the risks as well as the benefits of the new drug.
Per Olav Vandvik, professor of medicine at the University of Oslo, senior researcher at the Norwegian Institute of Public Health, and a member of The BMJ’s Rapid Recommendations guideline panel, said, “Recent guidelines from the European Society of Cardiology exemplify aggressive treatment strategies, with strong recommendations for large populations of patients to use yet another drug, with substantial budget implications for public health care systems. Although the evidence of efficacy and safety appear to be in place, the absolute benefits these drugs provide for individual patients is more questionable, and they do come on top of statins and ezetimibe, also likely adding to the burden of treatment for these patients.”
Naveed Sattar, professor of metabolic medicine at the University of Glasgow, said, “Doctors are excited by inclisiran and the potential to ‘vaccinate’ against high cholesterol in some patients, with obvious benefits to compliance and uptake. However, many would also like to see longer term safety data from ongoing trials and to be told the cost of this new drug before they consider implications for care.”