- ACRONYMS AND DEFINITIONS
- ASCVD - Atherosclerotic cardiovascular disease
- HeFH - Heterozygous familial hypercholesterolemia
- PCSK9 - Proprotein convertase subtilisin kexin type 9
- DRUGS IN CLASS
- Inclisiran is a small interfering ribonucleic acid (siRNA). It is currently the only drug of this type used to treat high cholesterol.
- MECHANISM OF ACTION
- Proprotein convertase subtilisin kexin type 9 (PCSK9)
- PCSK9 is an enzyme produced primarily in hepatocytes that is involved in cholesterol homeostasis. LDL receptors on the surface of liver cells facilitate the removal of LDL cholesterol from the blood. PCSK9 binds to LDL receptors and causes them to degrade. LDL receptor loss reduces LDL uptake by hepatocytes, and plasma LDL levels rise.
- Inclisiran is a double-stranded small interfering ribonucleic acid (siRNA), conjugated on the sense strand with triantennary N-Acetylgalactosamine (GalNAc) to facilitate uptake by hepatocytes. In hepatocytes, inclisiran utilizes the RNA interference mechanism and directs catalytic breakdown of mRNA for PCSK9. This increases LDL-C receptor recycling and expression on the hepatocyte cell surface, which increases LDL-C uptake and lowers LDL-C levels in the circulation.
- FDA-APPROVED INDICATION
- Inclisiran (Leqvio®)
- Heterozygous familial hypercholesterolemia (HeFH) - as an adjunct to diet and maximally-tolerated statin therapy in adults who require additional lowering of low-density lipoprotein cholesterol (LDL-C).
- Clinical atherosclerotic cardiovascular disease (ASCVD) - as an adjunct to diet and maximally-tolerated statin therapy in adults who require additional lowering of low-density lipoprotein cholesterol (LDL-C).
- CHOLESTEROL EFFECTS
|Lipid effects in patients with ASCVD on maximally tolerated statin|
|Lipid effects in patients with HeFH on maximally tolerated statin|
- SIDE EFFECTS
- Combined side effect data from 3 trials lasting 18 months are presented in the table below. Only side effects that occurred in at least 3% of inclisiran-treated patients and more than placebo are listed.
|Injection site reactions✝||8.2%||1.8%|
|Pain in extremity||3.3%||2.6%|
- Drug antibodies
- Biologic medications like inclisiran have the potential to induce a host immune response that leads to the production of antibodies that bind the drug. In some cases, these anti-drug antibodies reduce the drug's efficacy and/or increase the risk of hypersensitivity reactions. In other cases, they have no meaningful effect.
- In trials, up to 4.9% of inclisiran-treated patients developed anti-inclisiran antibodies. Antibody development was not associated with decreased efficacy or a higher risk of adverse events.
- None known
- Kidney disease
- No dose adjustment is necessary in mild, moderate, or severe renal impairment. It has not been studied in end-stage renal disease.
- Liver disease
- Child-Pugh A/B: no dose adjustment necessary
- Child-Pugh C: has not been studied
- DRUG INTERACTIONS
- NOTE: Drug interactions presented here are NOT all-inclusive. Other interactions may exist. The interactions presented here are meant to encompass commonly prescribed medications and/or interactions that are well-documented. Always consult your physician or pharmacist before taking medications concurrently. CLICK HERE for more information on drug interactions.
- Inclisiran (Leqvio®)
- No significant drug interactions are known
- Metabolism and elimination
- Inclisiran is primarily metabolized by nucleases to shorter nucleotides of varying length. Inclisiran is not a substrate for CYP450 or transporters.
- Dosage form
- 284 mg single-dose prefilled syringe
- Store at room temp
- Dosing: 284 mg administered as a single subcutaneous injection initially, again at 3 months, and then every 6 months
- Missed doses: If a planned dose is missed by less than 3 months, administer inclisiran and maintain dosing according to the patient’s original schedule. If a planned dose is missed by more than 3 months, restart with a new dosing schedule - administer inclisiran initially, again at 3 months, and then every 6 months.
- Inject subcutaneously into the abdomen, upper arm, or thigh. Injection should be administered by a healthcare professional.
- LDL effect is seen as early as 30 days after initiation
- LONG-TERM SAFETY
- Inclisiran was FDA-approved in 2021. It is the first drug in its class. There is no long-term safety data.
- 1 - Leqvio PI