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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.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\u003EResults from two Phase 2 trials indicate that intravenous infusions of RN316, a humanized IgG2?a monoclonal antibody that inhibits proprotein convertase subtilisin kexin type 9 (PCSK9), significantly lowers low-density lipoprotein cholesterol in hypercholesterolemic subjects already on high to maximal doses of statins.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ELipid Disorders\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EResults from two Phase 2 trials reported by Barry Gumbiner, MD, Pfizer, Inc., South San Francisco, California, USA, indicate that intravenous infusions of RN316, a humanized IgG2\u0394a monoclonal antibody that inhibits proprotein convertase subtilisin kexin type 9 (PCSK9), significantly lowers low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic subjects already on high to maximal doses of statins.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EAlthough statins are first-line therapy for reducing LDL-C and cardiovascular events, many patients are unable to achieve LDL-C goals or tolerate high doses of statin medication. PCSK9, a protein that reduces the number of LDL receptors, leading to diminished hepatic clearance capacity for plasma LDL-C and increased LDL-C levels, is a new therapeutic target for LDL-C lowering. RN316 binds to PCSK9, preventing PCSK9-mediated down-regulation of the LDL receptor, thereby improving LDL-C clearance and reducing LDL-C levels.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003ETwo Phase 2, randomized, double-blind, placebo-controlled, 12-week studies were conducted to assess the efficacy, safety, and tolerability of RN316 when added to high [A Multiple Dose Study of PF-04950615 (RN316) in Subjects on High Doses of Statins; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01342211\u0026amp;atom=%2Fspmdc%2F12%2F18%2F19.atom\u0022\u003ENCT01342211\u003C\/a\u003E] or maximum [A Multiple Dose Study of PF-04950615 (RN316) In Subjects On Maximum Doses of Statins; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01350141\u0026amp;atom=%2Fspmdc%2F12%2F18%2F19.atom\u0022\u003ENCT01350141\u003C\/a\u003E] doses of statins (atorvastatin, rosuvastatin, and simvastatin) in subjects with primary hypercholesterolemia. Subjects were eligible if they had an LDL-C \u2265100 mgdL in the high-dose statin study and \u226580 mg\/dL in the maximal-dose statin study. Subjects in the high-dose statin study were randomized to receive 0.25, 1.0, 3.0, or 6.0 mg\/kg doses of intravenous (IV) RN316 or placebo every 4 weeks, while those in the maximal-dose statin study were randomized to 1.0 or 3.0 mg\/kg of RN316 or placebo. RN316 dosing was interrupted if LDL-C reached \u226425 mg\/dL and resumed once it reached \u226540 mg\/dL at a later visit. Subjects were on average aged 55 to 61 years, and overweight or obese with an average body mass index of 30 kg\/m\u003Csup\u003E2\u003C\/sup\u003E.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EAcross the 5 arms, mean baseline LDL-C was \u223c123 mg\/dL, total cholesterol (TC) was \u223c197 mg\/dL, and HDL-C was \u223c49 mg\/dL. Triglycerides ranged from 115 mg\/dL to 173 mg\/dL. The primary endpoint was the mean percent change in lipid levels from baseline to Week 12.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EData were pooled from the 2 studies (n=135) for this analysis. LDL-C and TC decreased \u0026lt;15% in the placebo, and 0.25 mg\/kg and 1 mg\/kg RN316-dose groups, with reductions in LDL-C of 46% and 56% with 3- and 6-mg\/kg doses of RN316, respectively (p\u0026lt;0.001). For the 3- and 6-mg\/kg doses of RN316, there were also significant reductions in TC (30% and 37%, respectively [p\u0026lt;0.001]) and significant increases in HDL-C (7% and 11%, respectively [p\u0026lt;0.05]; \u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). There was no significant change in triglyceride levels. More than half of the subjects in the 3- and 6-mg\/kg dose groups had at least 1 interrupted dose (19 [59.4%] and 12 [70.6%], respectively). Without dose interruption, overall LDL-C lowering at Week 12 would have been similar to maximal LDL-C lowering observed at Week 4, as confirmed by the sustained LDL-C lowering of 75% in the 6-mg\/kg dose subgroup that had no dose interruption.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/18\/19\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Mean LDL-C Percent Change from Baseline.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-677050045\u0022 data-figure-caption=\u0022Mean LDL-C Percent Change from Baseline.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/18\/19\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/18\/19\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/18\/19\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13061\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\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EMean LDL-C Percent Change from Baseline.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EValues are mean \u00b1 SE; B1481005 and B1481012 data combined, modified ITT results; results include subjects who had dosing interrupted for LDL-C \u226425 mg\/dL; * p\u0026lt;0.05; **p\u0026lt;0.001\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced with permission from B Gumbiner, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-8\u0022\u003EApproximately two thirds of all subjects experienced adverse events (AEs) that were mild in nature and resolved without intervention; Dr. Gumbiner said that majority these were reported by the investigators as not likely to be related to the study drug. Overall AEs were balanced between the randomization groups. The development of antidrug antibodies (non-neutralizing) occurred in 5% of subjects receiving RN316, but there were no hypersensitivity reactions. Dr. Gumbiner concluded that overall RN316 appeared to be efficacious, safe, and well tolerated at the doses studied.\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\/18\/19.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_figures.js?nzn6ep\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_openurl.js?nzn6ep\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}