Inclisiran, the first RNA drug that reduces cholesterol, will be administered in Spain starting November 1, the pharmaceutical company Novartis has reported. The treatment is expected to significantly reduce the risk of suffering cardiovascular accidents such as strokes or heart attacks in people with excess cholesterol.
The European Medicines Agency (EMA) authorized inclisiran three years ago as a complement to usual treatment when this is not sufficient to reduce the level of LDL cholesterol in the blood to the recommended level. But the high price of the drug, which has not yet been made public but is expected to be around 3,000 euros per year per patient, prevents public health from being able to pay for it for the entire population for which it is indicated. In Spain, where it will be marketed under the name Leqvio, it will only be covered for now for people who have a higher risk of suffering a cardiovascular accident.
The treatment, which will be administered in hospitals, consists of a subcutaneous injection every six months. Its long-term effectiveness facilitates better cholesterol control than shorter-acting measures, in which adherence to treatment is not always optimal.
“One of the problems of treating cardiovascular risk factors is that they do not hurt, the actions are preventive and many people find it difficult to comply with the medication without feeling unwell. Inclisiran can help improve treatment compliance,” declares José María Mostaza, head of the Internal Medicine section at the La Paz hospital in Madrid and former president of the Spanish Atherosclerosis Society.
The key to the long-term effectiveness of inclisiran is in the way it works. It consists of a small strand of RNA that blocks the production of a protein in cells.
(If you are interested in the technical details, the RNA in inclisiran is coupled to a fragment of messenger RNA, which is the one that has the instructions to make the protein. In this way, it cancels the action of the messenger RNA and the production of the protein. That's why inclisiran is called a small interfering RNA, or siRNA.
In this case, inclisiran blocks the production of the PCSK9 enzyme, which the human body produces naturally and promotes a high level of LDL cholesterol. Once administered, inclisiran integrates into liver cells, where most of PCSK9 is produced, and remains active for six months, reports Lluía Masana, internist at the Sant Joan de Reus hospital and president of the Network of Lipid and Lipid Units. Arteriosclerosis of Catalonia.
The usual treatment to reduce LDL cholesterol is based on the combination of a statin (a drug that lowers cholesterol) and a healthy diet (it is especially recommended that it be rich in plant foods and low in saturated fats). But many people who have suffered a cardiovascular accident, and who are at high risk of suffering another, cannot lower the recommended level of 55 milligrams of LDL cholesterol per deciliter of blood with this treatment. Furthermore, 9% of those affected tolerate statins poorly, so they do not receive them at the doses in which they would be most effective.
For all these patients, drugs that act against the PCSK9 enzyme have been developed. The first, which were approved in the European Union in 2015, were antibodies that block the enzyme once it has been produced. They reduce the level of LDL cholesterol by approximately half, but have the drawback that they must be injected every two weeks. Although patients can inject the antibody at home themselves, they must go to a hospital every two or three months - the interval depends on the communities - to collect the doses that will have to be stored in a refrigerator. The cost of these antibodies in Spain is about 3,500 euros per year per patient.
The effectiveness of inclisiran is not superior to that of antibodies if the treatment is followed well, points out José María Mostaza. But it has the advantage that it makes it easier for the treatment, which must be chronic, to be carried out well. It is also expected that its price will be somewhat lower.
“If a patient has good control of their LDL cholesterol with antibodies, I would not recommend that they change. But if you tell me that it bothers you to inject yourself every two weeks, or that sometimes you forget, and that it is a problem for you to come to the hospital every two months to get the doses, as sometimes happens to us in the regions of Tarragona, where there are patients who come from very far away, then I would offer them the alternative of inclisiran,” declares Lluís Massana.
PCSK9 inhibitors are administered in Spain to people who have a history of atherosclerotic vascular diseases, such as heart attack, angina pectoris, ischemic stroke or peripheral vascular disease. This is the group that has a higher risk of suffering a cardiovascular accident. They are also offered to people with familial hypercholesterolemia who cannot reduce their LDL cholesterol to the appropriate level even if they have not had any previous episode of vascular disease, as they are also at high risk.
In all cases, PCSK9 inhibitors are administered as complements to other treatments, not as substitutes, so they must be accompanied by a healthy diet and, in most cases, a statin.
