{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T05:38:55Z","timestamp":1792820335021,"version":"4.5.0"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T00:00:00Z","timestamp":1614038400000},"content-version":"vor","delay-in-days":22,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Drugs"],"published-print":{"date-parts":[[2021,2]]},"DOI":"10.1007\/s40265-021-01473-6","type":"journal-article","created":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T10:03:21Z","timestamp":1614074601000},"page":"389-395","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":355,"title":["Inclisiran: First Approval"],"prefix":"10.1007","volume":"81","author":[{"given":"Yvette N.","family":"Lamb","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,23]]},"reference":[{"issue":"49","key":"1473_CR1","doi-asserted-by":"publisher","first-page":"16958","DOI":"10.1021\/ja505986a","volume":"136","author":"JK Nair","year":"2014","unstructured":"Nair JK, Willoughby JLS, Chan A, et al. Multivalent N-acetylgalactosamine-conjugated siRNA localizes in hepatocytes and elicits robust RNAi-mediated gene silencing. J Am Chem Soc. 2014;136(49):16958\u201361.","journal-title":"J Am Chem Soc"},{"issue":"1","key":"1473_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s40259-019-00399-6","volume":"34","author":"CA German","year":"2020","unstructured":"German CA, Shapiro MD. Small interfering RNA therapeutic inclisiran: a new approach to targeting PCSK9. BioDrugs. 2020;34(1):1\u20139.","journal-title":"BioDrugs."},{"key":"1473_CR3","unstructured":"European Medicines Agency. Leqvio 284\u00a0mg solution for injection in pre-filled syringe: summary of product characteristics. 2021. http:\/\/www.ema.europa.eu\/. Accessed 25 Jan 2021."},{"key":"1473_CR4","unstructured":"European Medicines Agency. Leqvio (inclisiran): an overview of Leqvio and why it is authorised in the EU. 2021. http:\/\/www.ema.europa.eu\/. Accessed 25 Jan 2021."},{"key":"1473_CR5","unstructured":"Novartis. Novartis receives EU approval for Leqvio\u00ae (inclisiran), a first-in-class siRNA to lower cholesterol with two doses a year [media release]. 11 Dec 2020. http:\/\/www.novartis.com\/."},{"issue":"16","key":"1473_CR6","doi-asserted-by":"publisher","first-page":"1520","DOI":"10.1056\/NEJMoa1913805","volume":"382","author":"FJ Raal","year":"2020","unstructured":"Raal FJ, Kallend D, Ray KK, et al. Inclisiran for the treatment of heterozygous familial hypercholesterolemia. N Engl J Med. 2020;382(16):1520\u201330.","journal-title":"N Engl J Med"},{"issue":"16","key":"1473_CR7","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1056\/NEJMoa1912387","volume":"382","author":"KK Ray","year":"2020","unstructured":"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;382(16):1507\u201319.","journal-title":"N Engl J Med"},{"key":"1473_CR8","unstructured":"Novartis. Novartis successfully completes acquisition of The Medicines Company, adding a potentially first-in-class, investigational cholesterol-lowering therapy inclisiran [media release]. 7 Jan 2020. http:\/\/www.novartis.com."},{"key":"1473_CR9","unstructured":"Pagliarulo N. FDA delays decision on Novartis cholesterol therapy [media release]. 21 Dec 2020. http:\/\/www.biopharmadive.com\/."},{"key":"1473_CR10","unstructured":"The Medicines Company, Alnylam Pharmaceuticals. The Medicines Company and Alnylam form strategic alliance to develop and commercialize RNAi therapeutics targeting PCSK9 for the treatment of hypercholesterolemia [media release]. 4 Feb 2013. http:\/\/www.themedicinescompany.com."},{"key":"1473_CR11","unstructured":"European Medicines Agency. Leqvio (inclisiran): CHMP public assessment report. 2021. http:\/\/www.ema.europa.eu\/. Accessed 25 Jan 2021."},{"issue":"1","key":"1473_CR12","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1056\/NEJMoa1609243","volume":"376","author":"K Fitzgerald","year":"2017","unstructured":"Fitzgerald K, White S, Borodovsky A, et al. A highly durable RNAi therapeutic inhibitor of PCSK9. N Engl J Med. 2017;376(1):41\u201351.","journal-title":"N Engl J Med"},{"issue":"11","key":"1473_CR13","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1016\/S0735-1097(20)32705-4","volume":"75","author":"KK Ray","year":"2020","unstructured":"Ray KK, Kallend D, Leiter L, et al. Effect of inclisiran on LDL-C reduction across different background lipid lowering treatments: analyses from ORION-11. J Am Coll Cardiol. 2020;75(11):2078.","journal-title":"J Am Coll Cardiol"},{"key":"1473_CR14","doi-asserted-by":"crossref","unstructured":"Ray KK, Wright S, Kallend D, et al. Inclisiran and cardiovascular outcomes: analyses from ORION-11 [abstract no. 1423-191]. J Am Coll Cardiol. 2020;75(11):238.","DOI":"10.1016\/S0735-1097(20)30865-2"},{"key":"1473_CR15","doi-asserted-by":"crossref","unstructured":"Wright RS, Kallend D, Ray KK, et al. Evaluation of LDL-C reductions by siRNA treatment with inclisiran in patients with diabetes mellitus, metabolic syndrome or neither [abstract no. 1360-102]. J Am Coll Cardiol. 2020;75 (11 Suppl 1):2005.","DOI":"10.1016\/S0735-1097(20)32632-2"},{"issue":"22","key":"1473_CR16","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.1161\/CIRCULATIONAHA.119.044431","volume":"141","author":"GK Hovingh","year":"2020","unstructured":"Hovingh GK, Lepor NE, Kallend D, et al. Inclisiran durably lowers low-density lipoprotein cholesterol and proprotein convertase subtilisin\/kexin type 9 expression in homozygous familial hypercholesterolemia: the ORION-2 pilot study. Circulation. 2020;141(22):1829\u201331.","journal-title":"Circulation"},{"issue":"15","key":"1473_CR17","doi-asserted-by":"publisher","first-page":"1430","DOI":"10.1056\/NEJMoa1615758","volume":"376","author":"KK Ray","year":"2017","unstructured":"Ray KK, Landmesser U, Leiter LA, et al. Inclisiran in patients at high cardiovascular risk with elevated LDL cholesterol. N Engl J Med. 2017;376(15):1430\u201340.","journal-title":"N Engl J Med"},{"issue":"11","key":"1473_CR18","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1001\/jamacardio.2019.3502","volume":"4","author":"KK Ray","year":"2019","unstructured":"Ray KK, Stoekenbroek RM, Kallend D, et al. Effect of 1 or 2 doses of inclisiran on low-density lipoprotein cholesterol levels: one-year follow-up of the ORION-1 randomized clinical trial. JAMA Cardiol. 2019;4(11):1067\u201375.","journal-title":"JAMA Cardiol."},{"key":"1473_CR19","unstructured":"The Medicines Company. New long-term data show that twice-a-year dosing with inclisiran results in persistent lowering of LDL cholesterol with no material safety observations out to three years [media release]. 20 May 2019. http:\/\/www.themedicinescompany.com."},{"key":"1473_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2020.08.018","author":"SA Khan","year":"2020","unstructured":"Khan SA, Naz A, Qamar Masood M, et al. Meta-analysis of inclisiran for the treatment of hypercholesterolemia. Am J Cardiol. 2020. https:\/\/doi.org\/10.1016\/j.amjcard.2020.08.018.","journal-title":"Am J Cardiol"},{"issue":"4","key":"1473_CR21","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1007\/s40256-018-0270-7","volume":"18","author":"Y Wang","year":"2018","unstructured":"Wang Y, Wang J, Wang S. Comparative effectiveness of inclisiran 100, 300, and 500\u00a0mg in a population with hyperlipidemia: a network meta-analysis of randomized controlled trials. Am J Cardiovasc Drugs. 2018;18(4):271\u201382.","journal-title":"Am J Cardiovasc Drugs."},{"key":"1473_CR22","unstructured":"Wright RS, Kallend D, Ray K, et al. ORION: a pooled analysis of phase III studies of inclisiran [conference presentation]. In: ACC (American College of Cardiology) Conference. 2020."},{"issue":"1","key":"1473_CR23","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.mayocp.2019.08.021","volume":"95","author":"RS Wright","year":"2020","unstructured":"Wright RS, Collins MG, Stoekenbroek RM, et al. Effects of renal impairment on the pharmacokinetics, efficacy, and safety of inclisiran: an analysis of the ORION-7 and ORION-1 studies. Mayo Clin Proc. 2020;95(1):77\u201389.","journal-title":"Mayo Clin Proc"}],"updated-by":[{"DOI":"10.1007\/s40265-021-01529-7","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T00:00:00Z","timestamp":1620864000000}}],"container-title":["Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40265-021-01473-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40265-021-01473-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40265-021-01473-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T12:46:52Z","timestamp":1627649212000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40265-021-01473-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2]]},"references-count":23,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,2]]}},"alternative-id":["1473"],"URL":"https:\/\/doi.org\/10.1007\/s40265-021-01473-6","relation":{"correction":[{"id-type":"doi","id":"10.1007\/s40265-021-01529-7","asserted-by":"object"}]},"ISSN":["0012-6667","1179-1950"],"issn-type":[{"value":"0012-6667","type":"print"},{"value":"1179-1950","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2]]},"assertion":[{"value":"23 February 2021","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2021","order":2,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":3,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":4,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1007\/s40265-021-01529-7","URL":"https:\/\/doi.org\/10.1007\/s40265-021-01529-7","order":5,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The preparation of this review was not supported by any external funding.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy. Yvette Lamb is a salaried employee of Adis International Ltd\/Springer Nature, and declares no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authorship and Conflict of interest"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval, Consent to participate, Consent to publish, Availability of data and material, Code availability"}}]}}