Pharmacological and clinical profile of inclisiran sodium, a long-acting LDL cholesterol lowering siRNA, LEQVIO for s.c. injection syringe 300 mg
Inclisiran sodium (Brand name: LEQVIO® for s.c. injection syringe 300 mg, hereinafter referred to as inclisiran), a small interfering ribonucleic acid (siRNA) product that targets the mRNA that encodes the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein was approved on September 25, 2...
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Veröffentlicht in: | Folia Pharmacologica Japonica 2024/07/01, Vol.159(4), pp.254-263 |
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description | Inclisiran sodium (Brand name: LEQVIO® for s.c. injection syringe 300 mg, hereinafter referred to as inclisiran), a small interfering ribonucleic acid (siRNA) product that targets the mRNA that encodes the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein was approved on September 25, 2023 for the indication of “Familial hypercholesterolemia, hypercholesterolemia” in Japan. Inclisiran is conjugated on the sense strand with triantennary N-acetylgalactosamine to facilitate uptake by hepatocytes. In vitro and in vivo pharmacology studies demonstrated the lowering effects of PCSK9 and LDL-C in hepatocytes and cynomolgus monkeys. It was considered unlikely to cause clinically significant risks due to toxicities arising from complementary binding to non-target RNA sequences (hybridization-dependent off-target effects). Clinical trials conducted globally including Japan in patients with familial hypercholesterolemia and hypercholesterolemia who did not reach the LDL-C target showed that inclisiran sodium 300 mg dosed at Day 1, Day 90 and then every 6 months demonstrated significant LDL-C reduction and the efficacy sustained long. The majority of patients achieved the guideline recommended LDL-C targets. Inclisiran sodium 300 mg was well tolerated and there were no specific safety concerns. Therefore, inclisiran is expected to be a new therapeutic option for the patients with familial hypercholesterolemia and hypercholesterolemia. |
doi_str_mv | 10.1254/fpj.24018 |
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Inclisiran is conjugated on the sense strand with triantennary N-acetylgalactosamine to facilitate uptake by hepatocytes. In vitro and in vivo pharmacology studies demonstrated the lowering effects of PCSK9 and LDL-C in hepatocytes and cynomolgus monkeys. It was considered unlikely to cause clinically significant risks due to toxicities arising from complementary binding to non-target RNA sequences (hybridization-dependent off-target effects). Clinical trials conducted globally including Japan in patients with familial hypercholesterolemia and hypercholesterolemia who did not reach the LDL-C target showed that inclisiran sodium 300 mg dosed at Day 1, Day 90 and then every 6 months demonstrated significant LDL-C reduction and the efficacy sustained long. The majority of patients achieved the guideline recommended LDL-C targets. Inclisiran sodium 300 mg was well tolerated and there were no specific safety concerns. Therefore, inclisiran is expected to be a new therapeutic option for the patients with familial hypercholesterolemia and hypercholesterolemia.</description><identifier>ISSN: 0015-5691</identifier><identifier>EISSN: 1347-8397</identifier><identifier>DOI: 10.1254/fpj.24018</identifier><identifier>PMID: 38945909</identifier><language>jpn</language><publisher>Japan: The Japanese Pharmacological Society</publisher><subject>Animals ; Cholesterol, LDL - blood ; Humans ; Hypercholesterolemia - drug therapy ; Hyperlipoproteinemia Type II - drug therapy ; Hyperlipoproteinemia Type II - genetics ; Proprotein Convertase 9 - genetics ; Proprotein Convertase 9 - metabolism ; RNA, Small Interfering - administration & dosage ; RNA, Small Interfering - pharmacology</subject><ispartof>Folia Pharmacologica Japonica, 2024/07/01, Vol.159(4), pp.254-263</ispartof><rights>2024 by The Japanese Pharmacological Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c1489-f8f0292bc14788effae26d91a33f152ea4a79f27acdaeeab8ec0d94711083eb03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38945909$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mikami, Tadayoshi</creatorcontrib><creatorcontrib>Fujiwara, Yukari</creatorcontrib><creatorcontrib>Akahori, Mizuki</creatorcontrib><creatorcontrib>Tomimatsu, Naoko</creatorcontrib><creatorcontrib>Tamaki, Yuko</creatorcontrib><title>Pharmacological and clinical profile of inclisiran sodium, a long-acting LDL cholesterol lowering siRNA, LEQVIO for s.c. injection syringe 300 mg</title><title>Folia Pharmacologica Japonica</title><addtitle>Nihon Yakurigaku Zasshi</addtitle><description>Inclisiran sodium (Brand name: LEQVIO® for s.c. injection syringe 300 mg, hereinafter referred to as inclisiran), a small interfering ribonucleic acid (siRNA) product that targets the mRNA that encodes the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein was approved on September 25, 2023 for the indication of “Familial hypercholesterolemia, hypercholesterolemia” in Japan. Inclisiran is conjugated on the sense strand with triantennary N-acetylgalactosamine to facilitate uptake by hepatocytes. In vitro and in vivo pharmacology studies demonstrated the lowering effects of PCSK9 and LDL-C in hepatocytes and cynomolgus monkeys. It was considered unlikely to cause clinically significant risks due to toxicities arising from complementary binding to non-target RNA sequences (hybridization-dependent off-target effects). Clinical trials conducted globally including Japan in patients with familial hypercholesterolemia and hypercholesterolemia who did not reach the LDL-C target showed that inclisiran sodium 300 mg dosed at Day 1, Day 90 and then every 6 months demonstrated significant LDL-C reduction and the efficacy sustained long. The majority of patients achieved the guideline recommended LDL-C targets. Inclisiran sodium 300 mg was well tolerated and there were no specific safety concerns. Therefore, inclisiran is expected to be a new therapeutic option for the patients with familial hypercholesterolemia and hypercholesterolemia.</description><subject>Animals</subject><subject>Cholesterol, LDL - blood</subject><subject>Humans</subject><subject>Hypercholesterolemia - drug therapy</subject><subject>Hyperlipoproteinemia Type II - drug therapy</subject><subject>Hyperlipoproteinemia Type II - genetics</subject><subject>Proprotein Convertase 9 - genetics</subject><subject>Proprotein Convertase 9 - metabolism</subject><subject>RNA, Small Interfering - administration & dosage</subject><subject>RNA, Small Interfering - pharmacology</subject><issn>0015-5691</issn><issn>1347-8397</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kcFu1DAQhi0EoqvSAy-AfASpWezY2cTHVWlLpYi2CLhGE2eceuXEi70r1FsvPfbKA_ZJ8GbLXmyN5_OnsX9C3nM253khP5v1ap5LxqtXZMaFLLNKqPI1mTHGi6xYKH5ETmK0LWNFmZcLwd-SI1EpWSimZuTvzR2EAbR3vrcaHIWxo9rZcSrWwRvrkHpD7ZhOow0w0ug7ux1OKVDnxz4DvbFjT-svNdV33mHcYPAu9f5g2DWi_f5teUrr89tfV9fU-EDjXM-TcIXppk---x2HVDD2_PD4_PA09O_IGwMu4snLfkx-Xpz_OPua1deXV2fLOtNcViozlWG5yttUlVWFxgDmi05xEMLwIkeQUCqTl6A7QIS2Qs06JUvOWSWwZeKYfNx700t_b9PozWCjRudgRL-NjWCl5KLgnCf00x7VwccY0DTrYAcI9w1nzS6JJiXRTEkk9sOLdtsO2B3I__-egOUeWMUN9HgAIGysdjipeKEaOa2T9NDTKbEGR_EPKF-dvQ</recordid><startdate>20240701</startdate><enddate>20240701</enddate><creator>Mikami, Tadayoshi</creator><creator>Fujiwara, Yukari</creator><creator>Akahori, Mizuki</creator><creator>Tomimatsu, Naoko</creator><creator>Tamaki, Yuko</creator><general>The Japanese Pharmacological Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20240701</creationdate><title>Pharmacological and clinical profile of inclisiran sodium, a long-acting LDL cholesterol lowering siRNA, LEQVIO for s.c. injection syringe 300 mg</title><author>Mikami, Tadayoshi ; Fujiwara, Yukari ; Akahori, Mizuki ; Tomimatsu, Naoko ; Tamaki, Yuko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1489-f8f0292bc14788effae26d91a33f152ea4a79f27acdaeeab8ec0d94711083eb03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>jpn</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Cholesterol, LDL - blood</topic><topic>Humans</topic><topic>Hypercholesterolemia - drug therapy</topic><topic>Hyperlipoproteinemia Type II - drug therapy</topic><topic>Hyperlipoproteinemia Type II - genetics</topic><topic>Proprotein Convertase 9 - genetics</topic><topic>Proprotein Convertase 9 - metabolism</topic><topic>RNA, Small Interfering - administration & dosage</topic><topic>RNA, Small Interfering - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mikami, Tadayoshi</creatorcontrib><creatorcontrib>Fujiwara, Yukari</creatorcontrib><creatorcontrib>Akahori, Mizuki</creatorcontrib><creatorcontrib>Tomimatsu, Naoko</creatorcontrib><creatorcontrib>Tamaki, Yuko</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Folia Pharmacologica Japonica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mikami, Tadayoshi</au><au>Fujiwara, Yukari</au><au>Akahori, Mizuki</au><au>Tomimatsu, Naoko</au><au>Tamaki, Yuko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacological and clinical profile of inclisiran sodium, a long-acting LDL cholesterol lowering siRNA, LEQVIO for s.c. injection syringe 300 mg</atitle><jtitle>Folia Pharmacologica Japonica</jtitle><addtitle>Nihon Yakurigaku Zasshi</addtitle><date>2024-07-01</date><risdate>2024</risdate><volume>159</volume><issue>4</issue><spage>254</spage><epage>263</epage><pages>254-263</pages><artnum>24018</artnum><issn>0015-5691</issn><eissn>1347-8397</eissn><abstract>Inclisiran sodium (Brand name: LEQVIO® for s.c. injection syringe 300 mg, hereinafter referred to as inclisiran), a small interfering ribonucleic acid (siRNA) product that targets the mRNA that encodes the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein was approved on September 25, 2023 for the indication of “Familial hypercholesterolemia, hypercholesterolemia” in Japan. Inclisiran is conjugated on the sense strand with triantennary N-acetylgalactosamine to facilitate uptake by hepatocytes. In vitro and in vivo pharmacology studies demonstrated the lowering effects of PCSK9 and LDL-C in hepatocytes and cynomolgus monkeys. It was considered unlikely to cause clinically significant risks due to toxicities arising from complementary binding to non-target RNA sequences (hybridization-dependent off-target effects). Clinical trials conducted globally including Japan in patients with familial hypercholesterolemia and hypercholesterolemia who did not reach the LDL-C target showed that inclisiran sodium 300 mg dosed at Day 1, Day 90 and then every 6 months demonstrated significant LDL-C reduction and the efficacy sustained long. The majority of patients achieved the guideline recommended LDL-C targets. Inclisiran sodium 300 mg was well tolerated and there were no specific safety concerns. Therefore, inclisiran is expected to be a new therapeutic option for the patients with familial hypercholesterolemia and hypercholesterolemia.</abstract><cop>Japan</cop><pub>The Japanese Pharmacological Society</pub><pmid>38945909</pmid><doi>10.1254/fpj.24018</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Cholesterol, LDL - blood Humans Hypercholesterolemia - drug therapy Hyperlipoproteinemia Type II - drug therapy Hyperlipoproteinemia Type II - genetics Proprotein Convertase 9 - genetics Proprotein Convertase 9 - metabolism RNA, Small Interfering - administration & dosage RNA, Small Interfering - pharmacology |
title | Pharmacological and clinical profile of inclisiran sodium, a long-acting LDL cholesterol lowering siRNA, LEQVIO for s.c. injection syringe 300 mg |
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