{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:08:49Z","timestamp":1789967329811,"version":"4.0.1"},"reference-count":19,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,3,22]],"date-time":"2017-03-22T00:00:00Z","timestamp":1490140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004328","name":"Genentech","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004328","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Cardiology"],"published-print":{"date-parts":[[2017,7]]},"abstract":"Background<\/jats:title>Proprotein convertase subtilisin\/kexin type 9 (PCSK9<\/jats:styled-content>) downregulates low\u2010density lipoprotein (LDL<\/jats:styled-content>) receptors, thereby leading to a rise in circulating LDL<\/jats:styled-content> cholesterol (LDL<\/jats:styled-content>\u2010C). RG7652<\/jats:styled-content> is a fully human monoclonal antibody against PCSK9<\/jats:styled-content>. This placebo\u2010controlled, phase 1 ascending\u2010dose study in healthy subjects evaluated the safety of RG7652<\/jats:styled-content> and its efficacy as a potential LDL<\/jats:styled-content>\u2010C\u2013lowering drug.<\/jats:p><\/jats:sec>Hypothesis<\/jats:title>Anti\u2010PCSK9<\/jats:styled-content> antibody therapy safely and effectively reduces LDL<\/jats:styled-content>\u2010C.<\/jats:p><\/jats:sec>Methods<\/jats:title>Subjects (N\u2009=\u200980) were randomized into 10 cohorts. Six sequential single\u2010dose cohorts received 10, 40, 150, 300, 600, or 800\u2009mg of RG7652<\/jats:styled-content> via subcutaneous injection. Four multiple\u2010dose cohorts received 40 or 150\u2009mg of RG7652<\/jats:styled-content> once weekly for 4 weeks, either with or without statin therapy (atorvastatin).<\/jats:p><\/jats:sec>Results<\/jats:title>Adverse events (AEs<\/jats:styled-content>) were generally mild; the most common AEs<\/jats:styled-content> were temporary injection\u2010site reactions. No serious AEs<\/jats:styled-content>, severe AEs<\/jats:styled-content>, AEs<\/jats:styled-content> leading to study\u2010drug discontinuation, or dose\u2010limiting toxicities were reported. RG7652<\/jats:styled-content> monotherapy reduced mean LDL<\/jats:styled-content>\u2010C levels by up to 64% and as much as 100\u2009mg\/dL<\/jats:styled-content> at week 2; the effect magnitude and duration increased with dose (\u226557\u2009days following a single RG7652<\/jats:styled-content> dose \u2265300\u2009mg). Exploratory analyses showed reduced oxidized LDL<\/jats:styled-content>, lipoprotein(a), and lipoprotein\u2010associated phospholipase A2<\/jats:styled-content> with RG7652<\/jats:styled-content>. Antidrug antibody against RG7652<\/jats:styled-content> tested positive in 2 of 60 (3.3%) RG7652<\/jats:styled-content>\u2010treated and in 4 of 20 (20.0%) placebo\u2010treated subjects. Simultaneous atorvastatin administration did not appear to impact the pharmacokinetic profile or lipid\u2010lowering effects of RG7652<\/jats:styled-content>.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Overall, RG7652<\/jats:styled-content> elicited substantial and sustained dose\u2010related LDL<\/jats:styled-content>\u2010C reductions with an acceptable safety profile and minimal immunogenicity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/clc.22687","type":"journal-article","created":{"date-parts":[[2017,3,23]],"date-time":"2017-03-23T04:31:20Z","timestamp":1490243480000},"page":"503-511","source":"Crossref","is-referenced-by-count":18,"title":["A phase 1 study to evaluate the safety and LDL<\/scp> cholesterol\u2013lowering effects of RG7652<\/scp>, a fully human monoclonal antibody against proprotein convertase subtilisin\/kexin type 9"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7940-8150","authenticated-orcid":false,"given":"Amos","family":"Baruch","sequence":"first","affiliation":[{"name":"Genentech Inc. 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South San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia P.C.","family":"Chiu","sequence":"additional","affiliation":[{"name":"Genentech Inc. South San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wu","sequence":"additional","affiliation":[{"name":"Genentech Inc. South San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Kirchhofer","sequence":"additional","affiliation":[{"name":"Genentech Inc. South San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Peterson","sequence":"additional","affiliation":[{"name":"Genentech Inc. South San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Davis Jr","sequence":"additional","affiliation":[{"name":"Genentech Inc. 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