inclisiran (Leqvio, ALN-PCS)
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Indications
- experimental siRNA to lower LDL cholesterol (FDA-approved December 2021)
- cardiovascular disease
- lowers LDL cholesterol in maximally-treated statin recipients[2]
Dosage
- initial injection 284 mg SC, then at 3 months, thereafter
- 300-500 mg injection every 6 months (Leqvio)
- 300 mg SC QD safe for up to 6 years[5]
- 0.40 mg/kg IV infusion (ALN-PCS)
Mechanism of action
More general terms
- PCSK9 inhibitor (ALN-PCS)
- short interfering double-stranded RNA; antisense oligonucleotide (siRNA, microRNA, miRNA)
References
- ↑ Fitzgerald K et al Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1 trial. The Lancet, Early Online Publication, 3 October 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24094767 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)61914-5/abstract
Fitzgerald K, White S, Borodovsky A et al. A highly durable RNAi therapeutic inhibitor of PCSK9. N Engl J Med 2016 Nov 13 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27959715 <Internet> http://www.nejm.org/doi/10.1056/NEJMoa1609243 - ↑ 2.0 2.1 Ray KK, Landmesser U, Leiter LA et al. Inclisiran in patients at high cardiovascular risk with elevated LDL cholesterol. N Engl J Med 2017 Mar 17; PMID: https://www.ncbi.nlm.nih.gov/pubmed/28306389
- ↑ Stiles S FDA Approves First-in-Class Inclisiran to Lower LDL-C. Medscape. December 22, 2021 https://www.medscape.com/viewarticle/965464
Larkin HD News From the Food and Drug Administration Injectable siRNA Approved for Lowering Cholesterol. JAMA. 2022;327(9):805. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35230412 https://jamanetwork.com/journals/jama/fullarticle/2789563 - ↑ Ray KK, Wright RS, Kallend D et al Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. N Engl J Med. 2020 Apr 16;382(16):1507-1519 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32187462 https://www.nejm.org/doi/10.1056/NEJMoa1912387
- ↑ 5.0 5.1 Wright RS, Koenig W, Landmesser U et al Safety and Tolerability of Inclisiran for Treatment of Hypercholesterolemia in 7 Clinical Trials. J Am Coll Cardiol. 2023 Dec 12;82(24):2251-2261. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38057066 Free article. https://www.sciencedirect.com/science/article/pii/S0735109723077392
- ↑ 6.0 6.1 Wright RS, Ray KK, Landmesser U et al Effects of Inclisiran in Patients With Atherosclerotic Cardiovascular Disease. A Pooled Analysis of the ORION-10 and ORION-11 Randomized Trials. Mayo Clinic Proceedings. 2024. August PMID: https://www.ncbi.nlm.nih.gov/pubmed/39093262 https://www.mayoclinicproceedings.org/article/S0025-6196(24)00167-8/fulltext