Leqvio (inclisiran) lowers LDL cholesterol by silencing the gene that produces a protein called PCSK9 in liver cells. Unlike statins, which block cholesterol production directly, Leqvio works one step upstream: it stops your liver from making a protein that would otherwise remove the receptors responsible for clearing “bad” cholesterol from your blood. The result is a 48% to 52% reduction in LDL cholesterol with just two injections per year after an initial ramp-up period.
How Leqvio Lowers Cholesterol at the Cellular Level
Your liver cells have receptors on their surface that grab LDL cholesterol particles out of your bloodstream and pull them inside for disposal. A protein called PCSK9 normally breaks down those receptors, which means fewer of them are available to clear cholesterol. The more PCSK9 your liver makes, the fewer cleanup receptors you have, and the higher your LDL stays.
Leqvio is a small interfering RNA, or siRNA. That’s a short, synthetic strand of genetic material designed to intercept and destroy the specific messenger molecule your liver cells use to build PCSK9. Think of it like intercepting a set of instructions before the factory can read them. Without those instructions, liver cells produce far less PCSK9. With less PCSK9 circulating, more LDL receptors survive on the surface of your liver cells, and they pull more cholesterol out of your blood.
To make sure Leqvio reaches the right cells, it’s attached to a sugar molecule called GalNAc. This sugar acts like a delivery tag, binding to a specific receptor found almost exclusively on liver cells. That targeting is what allows a small injection under the skin to home in on the liver rather than affecting other tissues. Once inside the liver cell, the siRNA gets to work silencing PCSK9 production for months, which is why dosing is so infrequent.
How It Differs From Other Cholesterol Drugs
Statins reduce cholesterol by blocking an enzyme the liver uses to manufacture cholesterol itself. Leqvio works through a completely different pathway: it doesn’t stop cholesterol production but instead helps your body clear more LDL from the bloodstream by preserving the receptors that do that job.
There are also injectable PCSK9 inhibitors (evolocumab and alirocumab) that block the PCSK9 protein after it’s already been made. Leqvio goes a step earlier, preventing the protein from being produced in the first place. The practical difference for patients is dosing frequency. Those older PCSK9 inhibitors require injections every two to four weeks and can be self-administered at home. Leqvio is given just twice a year (after the initial doses) but must be administered by a healthcare professional.
Dosing Schedule
Leqvio is given as a subcutaneous injection in the abdomen, upper arm, or thigh. The schedule has three phases:
- First dose: administered at your initial appointment
- Second dose: 3 months later
- Maintenance doses: every 6 months after that
Each injection is 284 mg. If you miss a scheduled dose by fewer than 3 months, you can receive it and stay on your original timeline. If you miss by more than 3 months, you restart the full sequence: an initial dose, another at 3 months, then every 6 months going forward. Because a healthcare professional administers every injection, each dose typically happens during an office visit.
How Much It Lowers LDL
In the three pivotal clinical trials (ORION-9, ORION-10, and ORION-11), patients receiving Leqvio saw an average LDL reduction of about 51% compared to placebo over roughly 17 months. The 2026 ACC/AHA cholesterol management guidelines cite an expected LDL reduction of 48% to 52%. That effect is on top of whatever reduction patients are already getting from statins or other therapies, since Leqvio is used as an add-on, not a replacement.
Who Is It For
Leqvio is approved for use alongside diet and statin therapy in specific groups. The 2026 ACC/AHA guidelines position it as a reasonable option in two main scenarios. First, adults with severe hypercholesterolemia (LDL at or above 190 mg/dL) who still have LDL above 100 mg/dL despite maximally tolerated statin therapy, with or without ezetimibe. Second, adults with established cardiovascular disease who are at very high risk and haven’t reached their LDL goal on statins alone, particularly if they can’t tolerate or access the older injectable PCSK9 inhibitors, or if they prefer less frequent dosing.
In both cases, Leqvio isn’t the first option tried. It’s added when statins and sometimes ezetimibe aren’t bringing LDL low enough on their own. The target for very high-risk patients is an LDL below 55 mg/dL.
Side Effects
Leqvio’s side effect profile is relatively limited. The only adverse reaction occurring in at least 3% of patients in clinical trials (and more often than with placebo) was injection site reactions, reported in about 8% of Leqvio patients compared to 2% on placebo. These reactions include pain, redness, and rash at the injection site. They were mild enough that only 0.2% of patients stopped treatment because of them.
No other side effects crossed the 3% threshold in the pivotal trials, which included over 1,800 patients in each group. That’s a notably clean safety profile for a cholesterol drug, though long-term data beyond the trial periods continues to accumulate.