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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EProprotein convertase subtilisin\/kexin type 9 serine protease (PCSK9) binds to low-density lipoprotein receptors (LDLRs) and plays a pivotal role in LDLR degradation [McKenney JM et al. \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E 2012]. This article discusses outcomes on the low-density lipoprotein cholesterol-lowering effects of SAR236553\/REGN727 (SAR236553), a highly specific, fully human monoclonal antibody to PCSK9 [Efficacy and Safety Evaluation of SAR236553 (REGN727) In Patients With Primary Hypercholesterolemia and LDL-Cholesterol on Stable Atorvastatin Therapy; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01288443\u0026amp;atom=%2Fspmdc%2F12%2F4%2F20.atom\u0022\u003ENCT01288443\u003C\/a\u003E].\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ELipid Disorders Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EProprotein convertase subtilisin\/kexin type 9 serine protease (PCSK9) binds to low\u2013density lipoprotein receptors (LDLRs) and plays a pivotal role in LDLR degradation [McKenney JM et al. \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E 2012]. James M. McKenney, PharmD, National Clinical Research, Inc., Richmond, Virginia, USA, reported outcomes on the low\u2013density lipoprotein cholesterol (LDL\u2013C)\u2013lowering effects of SAR236553\/REGN727 (SAR236553), a highly specific, fully human monoclonal antibody to PCSK9 [Efficacy and Safety Evaluation of SAR236553 (REGN727) In Patients With Primary Hypercholesterolemia and LDL\u2013Cholesterol on Stable Atorvastatin Therapy; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01288443\u0026amp;atom=%2Fspmdc%2F12%2F4%2F20.atom\u0022\u003ENCT01288443\u003C\/a\u003E].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThree prior Phase 1 studies of SAR236553 have shown that the monoclonal antibody to PCSK9 significantly reduces LDL\u2013C levels in healthy volunteers and in subjects with familial or nonfamilial hypercholesterolemia [Stein EA et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe current Phase 2 dose\u2013ranging study was a double\u2013blind, parallel\u2013group, placebo\u2013controlled, multicenter trial. It included patients aged 18 to 75 years with LDL\u2013C \u2265100 mg\/dL (2.59 mmol\/L) who were on stable\u2013dose atorvastatin at 10 mg, 20 mg, or 40 mg for \u22656 weeks. A total of 183 individuals were randomized to either subcutaneous placebo every 2 weeks (Q2W); SAR236553 at 50 mg, 100 mg, or 150 mg (Q2W); or SAR236553 at 200 mg and 300 mg once every 4 weeks (Q4W) with an alternating placebo injection at 2 weeks.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe primary objective of the study was to evaluate the safety and LDL\u2013C\u2013lowering effect of 12 weeks of treatment with SAR236553 versus placebo. The primary study endpoint was the percentage change in calculated LDL\u2013C from baseline (mean of Week \u22121 and Week 0) to Week 12.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EThe addition of SAR236553 resulted in a significant decrease in LDL\u2013C from baseline. A clear dose\u2013response relationship with respect to percentage of LDL\u2013C lowering for both Q2W and Q4W administration was demonstrated: 40%, 64%, and 72% with 50 mg, 100 mg, and 150 mg Q2W, respectively, and 43% and 48% with 200 and 300 mg Q4W. At Week 12, LDL\u2013C reduction with placebo was 5.1% (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). SAR236553 also increased the rate of achievement of LDL\u2013C goals (\u0026lt;70 mg\/dL) compared with placebo. Of note, LDL\u2013C reductions were generally unaffected by the baseline atorvastatin dose.\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/14003\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/14003\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/14003\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EChanges in LDL\u2013C from Baseline to Week 12 by Treatment Group (mITT Population).\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-9\u0022\u003ESAR236553 produced consistent and robust reductions in all other Apo B\u2013containing lipoproteins (\u003Ca id=\u0022xref-table-wrap-2-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T2\u0022\u003ETable 2\u003C\/a\u003E), with important decreases in lipoprotein(a)\u2014a finding that is consistent with the prior Phase 1 studies [Stein EA et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2012]. There was also a trend toward lower triglycerides and increases in high\u2013density lipoprotein cholesterol (HDL\u2013C) and Apo AI versus placebo\u2014findings that were not entirely explained by the direct mechanism of action of PCSK9 inhibition. The biweekly injections appeared to deliver a more sustained LDL\u2013C reduction over the Q4W dosing schedule.\u003C\/p\u003E\u003Cdiv id=\u0022T2\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/14004\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/14004\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/14004\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 2.\u003C\/span\u003E \n            \u003Cp id=\u0022p-10\u0022 class=\u0022first-child\u0022\u003EChanges in ApoB, Non\u2013HDL\u2013C, and Lp(a) from Baseline to Week 12 by Treatment Group (mITT Population).\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-12\u0022\u003ESAR236553 was well tolerated during the study, with no signs of persistent or prevalent clinical or laboratory adverse events, including those that were associated with hepatic and muscle assessments. One patient who was assigned to the 300\u2013mg Q4W regimen developed a rare complication, leukocytoclastic vasculitis, an inflammatory immune complex\u2013mediated vasculitis of small\u2013caliber blood vessels, although no similar reactions have been reported. No antidrug antibodies were observed 2 weeks before or after the incident.\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003EAccording to Dr. McKenney, these results support further evaluation of this novel biologic lipid\u2013lowering therapy in large, multicenter, randomized, controlled trials. Plans are underway to evaluate if PCSK9 antibody therapy can reduce adverse cardiovascular outcomes among an internationally diverse patient population who are taking a variety of different background lipid\u2013lowering therapies.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2012 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/12\/4\/20.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nznhip\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nznhip\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}