The Government is planning an innovative collaboration with the pharmaceutical company Novartis aimed at tackling cardiovascular disease, in which the NHS will conduct trials of an as yet unlicensed injectable alternative to statins.

Inclisiran is currently the first and only cholesterol-lowering therapy in the siRNA (small-interfering RNA) class. It is in Phase III clinical development and has not been approved by any regulatory authority. It is administered as an injection twice a year.

As a siRNA, inclisiran harnesses the body’s natural process of RNA interference to specifically prevent production of the PCSK9 protein in the liver. This enhances the liver’s ability to remove LDL-C from the bloodstream, thereby lowering LDL-C levels and preventing the build-up of plaque in the arteries.

Early results from clinical trials suggest that if inclisiran is given to 300,000 patients annually in the UK, it could help prevent 55,000 heart attacks and strokes, and has the potential of saving 30,000 lives in the next 10 years.

The results of the ORION-9 study, announced at the American Heart Association meeting in November 2019, showed inclisiran achieved a lowering of 50 per cent in LDL-C with time-adjusted reductions of 45 per cent sustained over 18 months in patients with heterozygous familial hypercholesterolemia. It also demonstrated an excellent safety profile, with no treatment-related liver or renal abnormalities

Large-scale trial

Heart disease is the second biggest cause of death in the UK, with over 3 million people suffering from atherosclerotic cardiovascular disease and 2.5 million currently relying on statins to lower their cholesterol.

The DHSC is presenting the collaboration with Novartis as an example of how the UK can facilitate large-scale prevention trials by addressing implementation and manufacturing issues early on through research funded by government.

The agreement could make a significant contribution towards meeting the NHS Long Term Plan commitment to preventing 150,000 cardiovascular deaths over 10 years.

Inclisiran will be studied as part of a large-scale clinical trial expected to start later this year. The five year trial will look at the use of the drug in primary prevention patients and will be the first in the world to treat such a patient population. The trial is being supported by the National Institute for Health Research (NIHR), which is funded by the DHSC.

EMA approval

Inclisiran was developed by The Medicines Company, which was bought by Novartis in November 2019. The memorandums of understanding that form the basis of the collaboration were agreed prior to the acquisition.

The drug is expected to file for regulatory approval with the European Medicines Agency (EMA) in the first quarter of 2020 as a preventative add-on treatment to statins for patients who have already been diagnosed with cardiovascular disease.

Upon approval and NICE assessment, the intention is that NHS England will agree a population-level commercial arrangement with Novartis to make inclisiran available to patients as soon as 2021.

Sir John Bell, professor of medicine at the University of Oxford’s medical science division, said: “The discovery and development of Inclisiran marks an important change in the approach to pharmaceutical interventions for public health. This program has introduced the use of health care system data from the NHS to dramatically reduce costs by rapidly identifying patient populations through health records.

Professor of medicine and epidemiology at the University of Oxford, Martin Landray, said: “The trial will provide both 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.”