An RNA injection costing more than 60 million, helping to lower blood fat, prevent stroke has just been approved by the British health agency

Patients with high cholesterol levels, those who have suffered a heart attack or stroke, and especially those who have not responded to cholesterol-lowering drugs, in the UK have recently had a new treatment option after the UK health authority. approved a drug called inclisiran made by Novatis Pharmaceuticals.

This is an injection that uses RNA-based gene technology. When entering the body, it will act directly to turn off a gene called PCSK9, which helps lower bad cholesterol (LDL) levels in the blood.

Unlike other lipid-lowering drugs that need to be taken daily, patients using inclisiran only need 2 injections per year. Each of these injections currently costs about £2,000, equivalent to more than VND 60 million.

The NHS estimates that at least 300,000 UK patients will receive inclisiran injections every year. About 30,000 lives will be saved thanks to its preventive effects on heart attacks and strokes.

Meindert Boysen, director of the UK’s Nice Center for Medical Technology Evaluation, said inclisiran would now represent a drug “change the game” in the field of treatment of blood lipids, cardiovascular disease and stroke.

The first widely licensed gene silencing therapy

We know that fatty blood or hypercholesterolemia is a condition that occurs when the level of bad cholesterol (LDL) in the blood exceeds the threshold of 4.1 mmol/L, which lowers the level of good cholesterol (HDL). Bad cholesterol is the main cause of plaque in the walls of blood vessels, which in the long run will lead to cardiovascular diseases and complications such as hypertension, coronary heart disease, cerebrovascular accident, stroke…

To help patients with high cholesterol control cholesterol, doctors may give them certain medications, such as statins, continuously for a few weeks. The drug regulates enzymes in the liver, inhibits cholesterol production and reabsorbs it through biochemical mechanisms.

However, there are some known patients with mutations in the liver, denoted PCSK9, that inhibit cholesterol reabsorption and appear to be unresponsive to statins and other cholesterol-lowering therapies.

Scientists have long known they must find a way to turn off or silence the PCSK9 gene to help these people treat cardiovascular disease. In addition, turning off the PCSK9 gene in healthy people also allows them to prevent future cardiovascular disease.

So if there is an injection that can do that, it will be a preventive therapy and a treatment for cardiovascular disease.

This effort was previously pursued by a pharmaceutical company called The Medicines. In 2019, they developed a drug, inclisiran, to do just this.

Inclisiran is essentially a synthetic version of small interfering RNA (siRNA). This is a special piece of RNA synthesized in the laboratory. When injected into the body, it travels to the liver, targeting and destroying the messenger mRNAs of the PCSK9 gene.

When the PCSK9 gene’s mRNAs are destroyed, it turns off the expression of this gene, releasing the production of LDL bad cholesterol receptors on the liver. This helps the liver to reabsorb more cholesterol, lowering blood fat levels.

Results from clinical trials show that injections containing inclisiran can reduce bad cholesterol levels by up to 55%. If used in combination with a statin, the effectiveness can be as high as 75-80%.

Professor Kausik Ray, director of the Royal Heart Disease Prevention Center, said inclisiran could help people with high cholesterol levels and a history of cardiovascular disease reduce their risk of stroke or heart attack over 10 years. from 29% to 20%.

In 2019, realizing the potential of this drug after The Medicines Company brought inclisiran to phase III clinical trials, pharmaceutical giant Novatis bought the entire company for $9.7 billion only. to get the right to trade it.

The deal puts Novatis ahead of AstraZeneca and Pfizer, who are also developing similar gene therapies aimed at cardiovascular disease.

In 2020, Novatis’ inclisiran was applied and licensed in Europe. And this year, it was approved for use in the UK and became the first gene-silencing drug to be approved outside of the country for the treatment of rare genetic disorders.

Future treatments for many other diseases

With the advantage of directly affecting the cause or origin of the disease, gene silencing drugs are also being developed for many other conditions, such as preventing side effects after kidney transplantation, heal skin scars, treat cancer including skin cancer, prostate cancer, brain cancer…

Researchers are also looking into whether gene silencing could work in the treatment of neurological and brain disorders, such as Huntington’s disease and Alzheimer’s disease.

These methods use the same technique as other existing drugs. They target a specific gene or protein and turn it off. But in the case of cancers because it is so complex, many different proteins may need to be targeted at the same time.

Even so, beyond the licensed inclisiran, we will still have to wait for other therapies to prove their effectiveness in clinical trials before they can be rolled out on a large scale.

Another challenge lies in the cost of these drugs, which are often very expensive. For example, inclisiran is sold by Novatis under the brand name Leqvio, even if the UK health agency reaches a discount agreement with the company, each of their injections will still cost up to 1987.36 British pounds, or more. 62 million VND.

However, in the future, as more pharmaceutical companies enter the gene silencing therapy market, the cost of these drugs is expected to be reduced to reach more patients.

Refer to Theguadian, Theconversation