Inclisiran

Inclisiran (brand name Leqvio) is used to lower LDL-C (low-density lipoprotein cholesterol) in adults with high blood cholesterol, and adults and children 12 years of age and older with heterozygous familial hypercholesterolemia (HeFH) or homozygous familial hypercholesterolemia (HoFH). It can be used first-line, as monotherapy (by itself) or given with other cholesterol medications, such as statins. Inclisirin is given by subcutaneous (under the skin) injection, 2 times a year, by a healthcare provider.

Inclisiran works through a unique mechanism that targets PCSK9 protein production. By interfering with mRNA translation, it allows more LDL-C receptors to remain active on liver cells, enhancing the removal of bad cholesterol from the bloodstream. Inclisiran belongs to the drug class called small interfering RNA (siRNA) molecules. It was the first siRNA to be developed.

Inclisiran gained FDA approval on December 22, 2021, under the brand name Leqvio. There is no generic.

Inclisiran is a subcutaneous injection administered by a healthcare provider with twice-yearly maintenance dosing.

It can be injected under the skin of the abdomen, upper arm, or thigh. Tell your healthcare provider about any skin conditions or areas of injury you may have, such as psoriasis, eczema, sunburn, skin rashes, inflammation, or skin infections.

Inclisiran injection is given as an initial dose, repeated in 3 months, and then administered every 6 months after that.

• Do not stop receiving this medication without talking to your healthcare provider, as your LDL cholesterol levels may increase.
• See How is Leqvio (inclisiran) injection administered? for more information.

This medicine is an adjunct (add-on) treatment to an improved diet and usually the maximum tolerated statin dose.

Do not receive inclisiran if you are allergic to inclisiran, Leqvio, or any inactive ingredients in the inclisiran injection. See below for a complete list of ingredients.

Tell your healthcare provider about all the medical conditions you have, especially tell them if you have:

• severe kidney disease or are receiving dialysis
• severe liver disease
• arthritis
• asthma, COPD, or breathing problems
• a history of urinary tract infections
• skin conditions such as psoriasis or eczema
• are pregnant or intending to become pregnant
• are breastfeeding or intending to breastfeed.

You should not receive an inclisiran injection if you are pregnant or children with under 12 years of age with HeFH or HoFH.

Pregnancy

Inclisiran should not be used during pregnancy because it may harm an unborn baby. Tell your healthcare provider immediately if you become pregnant while receiving inclisiran. There is a pregnancy safety study that monitors pregnancy outcomes in women exposed to Leqvio. You can report your pregnancy to Novartis at 1-888-669-6682.

Breastfeeding

It is not known if inclisiran passes into human breast milk. Talk to your healthcare provider about the best way to feed your baby if you are having treatment with inclisiran.

The most common side effects of inclisiran are:

• injection site reactions, such as redness, pain, or bruising, where the injection was given
• joint pain
• bronchitis, colds in your chest, or breathing problems
• headache (in children 12 years of age and older).

Weight gain has not been reported as a side effect of inclisiran in clinical trials.

Serious side effects and warnings

Inclisiran may cause serious side effects, such as allergic reactions. Get emergency medical help if you have signs of an allergic reaction: hives, severe itching, difficulty breathing, swelling of your face, lips, tongue, or throat.

Inclisiran may increase your risk of urinary tract infections. Symptoms may include pain or burning while you are urinating, having to pass urine more frequently or more urgently than is usual for you, pelvic or rectal pain, or urine that is discolored or has a strong odor. Call your healthcare provider at once if you have any of these symptoms.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

The cost of inclisiran depends on what type of insurance you have and your eligibility for the Leqvio Copay card. In general, inclisiran is broadly covered and affordable for most patients because it is given by your doctor and is covered primarily under the medical benefit, not the pharmacy benefit.

• 75% of people with commercial insurance pay less than $10 for inclisiran, with just over 50% paying $0.
• 92% of patients with an insurance plan have medical benefits confirmed for inclisiran.
• Patients with traditional Medicare and supplemental insurance pay as little as $0.
• No matter what insurance you have, the Leqvio (inclisiran) Service Center can help you understand the costs associated with inclisiran.

See Leqvio (inclisiran) Prices, Coupons, Copay Cards, & Patient Assistance for more information.

Dose of Inclisiran for hypercholesterolemia in adults, or HeFH or HoFH in adults and children 12 years and older

• Dose 1: 284 mg SC
• Dose 2 (3 months later): 284 mg SC
• Dose 3 (6 months later and every 6 months thereafter): 284 mg SC.

Inclisiran is available in a single-dose prefilled syringe containing inclisiran (generic name) 284 mg/1.5 mL (189 mg/mL).

If you miss a dose of inclisiran and it has been less than 3 months, then see your healthcare provider for a dose and continue with your original dosing schedule.

If you miss a dose of this medicine and it has been more than 3 months, then see your healthcare provider and restart with a new dosing schedule - starting with an initial dose, then another dose at 3 months, and then every 6 months after that.

There is no specific treatment for an overdose of this medicine. If you receive too much, your healthcare provider will check you for side effects and treat any side effects as required.

Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Inclisiran is not expected to cause drug-drug interactions or to be affected by inhibitors or inducers of cytochrome P450 enzymes or transporters.

Inclisiran is stored by your healthcare provider at room temperature, 20°C to 25°C (68°F to 77°F).

• Excursions are permitted between 15°C and 30°C (59°F and 86°F).
• Do not freeze

For single-use only.

Active ingredient: inclisiran sodium 284 mg (present as 300 mg inclisiran sodium salt).

Inactive ingredients: Water for Injection and may also contain sodium hydroxide or phosphoric acid for pH adjustment to a target pH of 7.0.

Available as a 284 mg/1.5 mL (189 mg/mL) single-dose prefilled syringe.

Contains no preservatives.

Inclisiran (Leqvio) is manufactured by Novartis Pharmaceuticals Corporation, which is based in East Hanover, New Jersey, with global headquarters in Basel, Switzerland. The medication was developed under license from Alnylam Pharmaceuticals, Inc.

Novartis was formed in 1996 through the merger of Ciba-Geigy and Sandoz.