Key Points:<\/p>\n
<\/p>\n
Lipoprotein(a) is a critical, genetically-determined risk factor for cardiovascular disease without any currently approved pharmacological therapies. Lepodisiran is a novel siRNA therapy which is designed to degrade the mRNA which encodes the protein apoloprotein(a). In a breaking presentation at the 2023 AHA Scientific Sessions today, <\/span>Dr. Steven Nissen (Cleveland Clinic)<\/span><\/a> and his team presented their study: <\/span>\u201cLepodisiran: An Extended-Duration siRNA Targeting Lipoprotein(a).\u201d<\/span><\/a><\/p>\n This study enrolled 48 participants between age 18-65 without known cardiovascular disease with an elevated Lp(a)\u226575 nmol\/L (or \u2265 30 mg\/dL) . Participants were admitted to a Clinical Research Unit for monitoring a day prior to dosing and were monitored for three days after administration. Six participants apiece were randomized to a single dose of lepodisiran (ranging from 4mg to 608mg), and 12 participants were assigned to placebo. Participants were followed up to 48 weeks after dose administration. Key safety outcomes included emergent adverse events and injection site reactions and safety laboratory parameters. Lepodisiran plasma concentrations throughout 48 hours and Lp(a) concentrations through 48 weeks were also monitored.<\/span><\/p>\n The median age was 50, with 40% women. Lepodisiran plasma concentrations peaked between 9-15 hours across all doses. The maximal median change from baseline in serum lipoprotein(a) concentrations was \u22125% in the placebo group, \u221241% in the 4 mg dose\u00a0 group, \u221259% in the 12-mg dose group, \u221276% in the 32-mg dose group, \u221290% in the 96-mg dose group, \u221296% in the 304-mg dose group, and \u221297% in the 608-mg dose group. At day 337, the median change in lipoprotein(a) was \u221294% in the 608-mg dose group. While safety can not be comprehensively determined in such a small trial, lepodisiran appeared to be well-tolerated, as only a single serious adverse event occurred.<\/span><\/p>\n When discussing the clinical implications of the study at the Scientific Sessions, Dr. Nissen stated: \u201cSubcutaneous injection of lepodisiran, an siRNA targeting mRNA for the LPA gene substantially lowered lipoprotein(a)\u2026 serum concentrations of lipoprotein(a) and remained >94% below baseline for 337 days (48 weeks)\u2026these findings support further development of this therapy.\u201d<\/span><\/p>\n","protected":false},"excerpt":{"rendered":" Key Points: There are currently no approved targeted therapies for the reduction of Lp(a). In this Phase I study, a novel siRNA therapy (lepodisiran) was tested in escalating doses and compared to placebo in 48 patients. Lp(a) concentrations and safety events were examined for 48 weeks. Single-dose lepodisiran administration resulted in up to 94% reduction […]<\/p>\n","protected":false},"author":40603,"featured_media":10839,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[883,18,8],"tags":[885,45,47,185],"ppma_author":[1029],"class_list":{"0":"post-138155","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-aha-2023","8":"category-lipid-lowering-therapy","9":"category-news","10":"tag-aha-2023","11":"tag-conference","12":"tag-featured","13":"tag-news","14":"author-leah-kosyakovsky"},"authors":[{"term_id":1029,"user_id":40603,"is_guest":0,"slug":"leah-kosyakovsky","display_name":"Leah Kosyakovsky","avatar_url":"https:\/\/secure.gravatar.com\/avatar\/864bde69f6f1f80e91e4a97f0a0ba8daa64c2bb702be09ed787444c7dfa045bb?s=96&r=g","0":null,"1":"","2":"","3":"","4":"","5":"","6":"","7":"","8":""}],"_links":{"self":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/138155","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/users\/40603"}],"replies":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=138155"}],"version-history":[{"count":1,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/138155\/revisions"}],"predecessor-version":[{"id":138156,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/138155\/revisions\/138156"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/media\/10839"}],"wp:attachment":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=138155"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=138155"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=138155"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=138155"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}