@prefix rdf: . @prefix xsd: . @prefix skos: . @prefix itsrdf: . @prefix nif: . nif:beginIndex "0"^^xsd:nonNegativeInteger ; nif:endIndex "2557"^^xsd:nonNegativeInteger ; nif:firstSection , ; nif:hasSection , , , , , ; nif:isString "Mipomersen (previously ISIS 301012, trade name Kynamro) is a cholesterol-reducing drug. It is an antisense therapeutic that targets the messenger RNA for apolipoprotein B. It is administered as a weekly injection for familial hypercholesterolemia.\n\nIndications\nKynamro is FDA approved to treat homozygous familial hypercholesterolemia (HoFH). It reduces LDL-C, non HDL-C, and apolipoprotein B. Over a 26-week trial LDL decreased 25%. The FDA decided on a boxed warning of liver toxicity and requires cerfiication by the prescriber and pharmacy. Mipomersen decreases hepatic and plasma apoB as well as apoC-III.\n\nChemical properties\nThe compound is a 'second-generation' antisense oligonucleotide; the nucleotides are linked with phosphorothioate linkages rather than the phosphodiester linkages of RNA and DNA, and the sugar parts are deoxyribose in the middle part of the molecule and 2'-O-methoxyethyl-modified ribose at the two ends. These modifications make the drug resistant to degradation by nucleases, allowing it to be administered weekly. The drug accumulates in the liver, which is convenient since apolipoprotein B predominantly acts there. The complete sequence is G*-C*-C*-U*-C*-dA-dG-dT-dC-dT-dG-dmC-dT-dT-dmC-G*-C*-A*-C*-C* [d = 2'-deoxy, * = 2'-O-(2-methoxyethyl)] with 3'→5' phosphorothioate linkages.\n\nClinical development\nThe drug was discovered and developed to Phase 2 by ISIS Pharmaceuticals and subsequently licensed to Genzyme Corporation in 2008 by an auction bid. Isis earned an upfront payment of $325 million, with payments of a further $825 million if milestones are met. In January 2013, The United States Food and Drug Administration approved mipomersen for the treatment of homozygous familial hypercholesterolemia. Launch quantities will be manufactured by Isis at their Carlsbad manufacturing facilities.\n\nReferences\n\n\nExternal links\n\n* Phase III trials of Mipomersen \n* Phase 3 results from Isis Pharmaceuticals" ; nif:lastSection , ; nif:predLang ; nif:sourceUrl . a nif:Title ; nif:anchorOf "References" ; nif:beginIndex "2451"^^xsd:nonNegativeInteger ; nif:endIndex "2461"^^xsd:nonNegativeInteger ; nif:referenceContext ; nif:superString . a nif:Phrase ; nif:anchorOf "apolipoprotein B" ; nif:beginIndex "1110"^^xsd:nonNegativeInteger ; nif:endIndex "1126"^^xsd:nonNegativeInteger ; nif:referenceContext ; nif:superString ; itsrdf:taIdentRef . a nif:Title ; nif:anchorOf "Chemical properties" ; nif:beginIndex "612"^^xsd:nonNegativeInteger ; nif:endIndex "631"^^xsd:nonNegativeInteger ; nif:referenceContext ; nif:superString . a nif:Phrase ; nif:anchorOf "homozygous familial hypercholesterolemia" ; nif:beginIndex "2343"^^xsd:nonNegativeInteger ; nif:endIndex "2383"^^xsd:nonNegativeInteger ; nif:referenceContext ; 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