Inclisiran, the first RNA drug that reduces cholesterol, will be administered in Spain from November 1, the pharmaceutical company Novartis has announced. The treatment is expected to significantly reduce the risk of stroke or heart attack in people with excess cholesterol.
The European Medicines Agency (EMA) authorized inclisiran three years ago as a supplement to usual treatment when it is not enough to reduce the level of LDL cholesterol in the blood to the recommended level. 10% of the Spanish adult population is in this situation, according to data from the Enrica study published in 2011, the most recent available.
But the high price of the drug, which has not yet been made public but will predictably 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 having 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 drugs, in which adherence to treatment is not always optimal.
“One of the problems with treating cardiovascular risk factors is that they do not cause symptoms and many people find it difficult to comply with their medication when they are not unwell. Inclisiran can help improve treatment compliance," says José María Mostaza, head of the Internal Medicine section at La Paz Hospital in Madrid and former president of the Spanish Society of Arteriosclerosis.
The key to inclisiran's long-term effectiveness is the way it works. It consists of a small chain of RNA that blocks the production of a protein in cells.
(If you're interested in the technical details, the RNA in inclisiran binds to a piece of messenger RNA, which is the one that has the instructions for making the protein. In this way, it overrides the action of the ' messenger RNA and the production of the protein. That's why inclisiran is a type of drug called small interfering RNA, or a siRNA, by its initials in English.)
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 Lluís Masana, internist at Sant Joan de Reus hospital and president of the Network of Lipids and Arteriosclerosis Units of Catalonia.
The usual treatment to lower LDL cholesterol is based on the combination of a statin (a drug that lowers cholesterol) and a healthy diet (high in plant foods and low in saturated fat is recommended). But a large proportion of people who have had a heart attack, and who are at high risk of another one, fail to lower their LDL cholesterol to the recommended level of 55 milligrams per deciliter of blood with this treatment. 9% of those affected, in addition, tolerate statins poorly, so they do not receive them at the doses in which they would be most effective.
Drugs that act against the PCSK9 enzyme have been developed for all these patients. The first, which were approved in the European Union in 2015, were antibodies that block the enzyme when it has already been produced. They reduce the level of LDL cholesterol by approximately half, but have the disadvantage 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 to three months to collect doses that will need to be kept in a refrigerator. The cost of these antibodies in Spain is around 3,500 euros per patient per year.
The effectiveness of inclisiran is not superior to that of antibodies if the treatment is followed well, notes José María Mostaza. But it has the advantage of making it easier for the treatment, which must be chronic, to be carried out. It is also expected that its price will be a little lower.
“If a patient has good LDL cholesterol control with antibodies, I wouldn't recommend switching. But if he tells me that it bothers him to inject himself every two weeks, or that he sometimes forgets, and that it is a problem for him to come to the hospital every two months to get the doses, as happens in the regions of Tarragona, where there are patients who come from far away, then I would offer them the alternative of inclisiran", declares Lluís Masana.
PCSK9 inhibitors are administered in Spain to people who have a history of arteriosclerotic vascular diseases, such as heart attack, angina pectoris, ischemic stroke or peripheral vascular disease. This is the group that has a higher risk of having a cardiovascular accident. They are also offered to people with familial hypercholesterolemia who fail to reduce LDL cholesterol to the appropriate level, as they are also at high risk. PCSK9 inhibitors are given as adjuncts to other treatments, not as substitutes, and therefore must be accompanied by a healthy diet and, in most cases, a statin.
