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FDA Approves a New RNA-Based Treatment to Lower Cholesterol

Leqvio uses RNA to help keep levels of LDL cholesterol in the blood low and requires only two doses per year.

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Illustration: Novartis

The Food and Drug Administration has approved a novel type of cholesterol-lowering drug jointly developed by Alnylam Pharmaceuticals and Novartis. The treatment, called Leqvio, uses RNA to help keep levels of low-density lipoprotein (LDL) cholesterol in the blood low, which is important for people with certain cardiovascular diseases. The injectable therapy will supplement diet and other cholesterol drugs known as statins, and will only need to be taken as infrequently as twice a year.

RNA, along with DNA, is a type of genetic information that has several different functions in biology. One of these roles is to serve as a messenger (mRNA), relaying instructions to cells so that they can produce important proteins and other components. A now well-known example of this function comes from the mRNA-based covid-19 vaccines. An injection of the vaccine tells the body’s cells how to produce a key but incomplete part of the coronavirus, which then trains the immune system to recognize the virus, without actually causing an infection.


But there’s another form of RNA called small interfering RNA (siRNA), which acts as a sort of counterbalance to mRNA. siRNA will tell the body’s cells to degrade a specific bit of mRNA, preventing the cell from carrying out the genetic instructions contained in that mRNA. This is a normal part of our biology, but as with mRNA, scientists have been hopeful about the possibility of creating synthetic bits of siRNA for medical purposes.

In Leqvio’s case, the siRNA has been crafted to reduce the production of a protein from our liver’s cells—a protein that’s important for regulating levels of LDL circulating in our blood (LDC-C). Constantly high LDL-C cholesterol, often known as the “bad” cholesterol, is thought to contribute to arteriosclerosis, or the hardening of our arteries, which can then raise the risk of heart attacks and strokes. Lowering LDL-C is thought to lower the risk of these complications.


Leqvio was initially discovered by Alnylam Pharmaceuticals, and further developed in partnership with Novartis. It was tested in three clinical trials of nearly 3,500 patients with arteriosclerosis along with patients who had heterozygous familial hypercholesterolemia (HeFH), a hereditary condition that causes very high cholesterol levels. These patients were already on the maximum dose of statins, a long-used treatment for reducing cholesterol, that they could tolerate. Compared to the placebo group, levels of LDL-C dropped by 52% on average for Leqvio users after 17 months. Common adverse events associated with the treatment included joint stiffness, urinary tract infection, diarrhea, bronchitis, and injection site pain. A theoretical risk of siRNA-based therapies—triggering an immune response against the drug that could affect its success or cause other adverse effects—doesn’t appear to have been seen in trials, the FDA noted, though long-term safety data will be needed to keep an eye on that.

The drug will only be prescribed as an add-on to diet and statin medication for people with arteriosclerosis or HeFH who still have too-high levels of LDL-C. Patients will get the first two subcutaneous injections three months apart, then every six months, at a doctor’s office. As with other cholesterol-lowering drugs, Leqvio will not be recommended for people who are pregnant.

siRNA therapy has been previously approved to treat some genetic disorders. But this is the first drug of its type to be approved for lowering cholesterol, and it’s likely to have a much wider patient base. HeFH is a rare disease, but millions of Americans with arteriosclerosis who are taking statins still have higher-than-healthy levels of LDL.

One important test for Leqvio will be whether its use actually leads to fewer cardiovascular events and longer life expectancy, a question that the clinical trial data wasn’t able to answer definitively.


Assuming Leqvio is as successful as Novartis hopes, though, it may signal a new frontier of medicine, following in the footsteps of mRNA vaccines. Other siRNA-based therapies are being tested out in Phase III trials for a variety of medical conditions, including kidney injury, hemophilia, and certain chronic eye disorders.