Inclisiran

Inclisiran is a PCSK9 inhibitor based on siRNA interference that is used as a lipid-lowering agent for LDL-C reduction.

It is the first and so far only siRNA interference therapy that has been approved for LDL-C lowering.

Inclisiran, in combination with statins and other lipid-lowering drugs, enables effective LDL-C reduction to very low target values even in cases of high cardiovascular risk and, by administering it every 6 months, ensures sustained therapeutic success and a high degree of therapy adherence in the long term.

According to current data, Inclisiran is generally well tolerated.

The only known side effects to date are reactions (pain, erythema, rash) at the injection site. These were often mild to moderate, transient and resolved without sequelae.

Immunogenicity:
Anti-drug antibodies were found in RCT in 1.8%
(33/1,830) of patients prior to treatment initiation and 4.9% (90/1,830) of patients during 18 months of treatment with inclisiran; no clinically relevant differences in the clinical efficacy, safety or pharmacodynamic profile of inclisiran were observed.

Laboratory values:
Elevations of serum transaminases between > 1x the upper limit of normal (ULN) and ≤ 3x ULN were found more frequently in RCTs; however, they did not exceed the clinically relevant threshold of ≥3 times the upper limit of normal, were asymptomatic, and were not associated with adverse reactions or other signs of liver dysfunction.

Reporting of suspected adverse reactions:

Inclisiran is subject to increased pharmacovigilance. Side effects occurring during treatment should be reported immediately via nebenwirkungen.bund.de.

1. Ference BA, Robinson JG, Brook RD et al (2016). Variation in PCSK9 and HMGCR and Risk of Cardiovascular Disease and Diabetes. N Engl J Med 375:2144-53. doi/full/10.1056/NEJMoa1604304
2. Raal FJ, Kallend D, Kausik K R et al. for the ORION-9 Investigators (2020). Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia. N Engl J Med 382:1520-30. doi/full/10.1056/NEJMoa1913805
3. Ray KK, Wright RS, Kallend D, Koenig W, et al for the ORION-10 and ORION-11 Investigators. (2020). Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. N Engl J Med 382:1507-1519 doi/full/10.1056/NEJMoa1912387.
4. Ray KK, Troquay RPT, Visseren FLJ et al (2023). Long term efficacy and safety of inclisiran in patients with high cardiovascular risk and elevated LDL cholesterol (ORION-3): results from the 4-year open-label extension of the ORION-1 trial. Lancet Diabetes Endocrinol. 11(2):109-119. doi.10.1016/S2213-8587(22)00353-9
5. Wright RS, Raal FJ, Koenig W et al (2024). Inclisiran administration potently and durably lowers LDL-C over an extended-term follow-up: the ORION-8 trial. Cardiovasc Res. 120 (12):1400-1410. doi: 10.1093/cvr/cvae109.

Expert information Inclisiran: ^Leqvio® 284 mg solution for^injection®