{"id":137922,"date":"2023-03-08T09:09:37","date_gmt":"2023-03-08T14:09:37","guid":{"rendered":"https:\/\/cardiologynownews.org\/?p=137922"},"modified":"2023-03-08T09:09:37","modified_gmt":"2023-03-08T14:09:37","slug":"a-novel-oral-psck-9-inhibitor-showed-significant-and-dose-dependent-reduction-of-ldl-compared-to-placebo","status":"publish","type":"post","link":"https:\/\/cardiologynownews.org\/?p=137922","title":{"rendered":"A Novel, Oral, PSCK-9 Inhibitor Showed Significant and Dose-dependent Reduction of  LDL compared to Placebo"},"content":{"rendered":"<p><strong>Key Points\u00a0<\/strong><\/p>\n<p>-Lowering LDL-C is known to reduce the risk of ASCVD<\/p>\n<p>-In patients at very high risk for ASCVD or in those with intolerance to statins, PCSK-9 inhibitors are recommended, however, current PCSK-9 inhibitors are administered subcutaneously, limiting their use<\/p>\n<p>-The findings of this Phase 2 trial suggest that MK-0616, an oral PCSK-9 inhibitor significantly reduced LDL-C at 8 weeks by as much as 60.3% compared to placebo<\/p>\n<p><!--more--><\/p>\n<p><strong>Introduction<\/strong><\/p>\n<p>Hypercholesterolemia is a major risk factor for atherosclerotic cardiovascular disease (ASCVD) and treatment focuses on lowering low density lipid cholesterol (LDL-C). While statins are the mainstay for treating hypercholesterolemia, there is a growing role for proprotein convertase subtilisin\/kexin type (PCSK) 9 inhibitors. PCSK-9 inhibitors are especially useful in patients on maximally tolerated statin and very high ASCVD risk who require further LDL-C reduction and in those with intolerance to statins. One barrier to patients adopting the use of PCSK9 inhibitors is that they are injectable.<\/p>\n<p>&nbsp;<\/p>\n<p>PCSK-9 inhibitors reduce cholesterol levels by preventing the degradation of LDL-C receptors on the surface of hepatocytes, thereby promoting clearance of LDL-C from plasma. The results of a trial (NCT05261126) evaluating a new, daily, oral PSCK-9 inhibitor\u00a0 in reducing LDL-C in subjects with hypercholesterolemia was presented by Dr. Christie Ballantyne (Baylor College of Medicine, Houston, TX) at ACC 2023 conference this afternoon.<\/p>\n<p>&nbsp;<\/p>\n<p>A total of 381 participants with a wide range of ASCVD risk were enrolled in this randomized, double-blind, placebo-controlled trial. There were five treatment arms; four escalating doses (6mg, 12mg, 18mg, or 30mg) of the oral PSCK-9 inhibitor, MK-0616, and placebo. The primary outcome was LDL-C level change from baseline to 8 weeks. Eligible participants had a history of stable background statin therapy including no statin,\u00a0clinical ASCVD or\u00a010-year risk of event \u2265 5%. Subjects with a history of homozygous familial hypercholesterolemia, impaired renal function, or a major cardiovascular event within 3 months were excluded. The median age of the participant was 62 years, 49% female, 66% white, the average LDL-C was 119.5mg\/dL, and 38.6% had clinical ASCVD.<\/p>\n<p>&nbsp;<\/p>\n<p>All four doses of MK-0616 resulted in significant reductions in LDL-C, with the highest dose\u00a0(30mg) resulting in a 60.9% placebo-adjusted reduction at eight weeks. Furthermore, at the highest dose, MK-0616 reduced ApoB by 51.8%\u00a0 and non-HDL-C\u00a0 by 55.8%, and 90.8% participants met their LDL-C goal (defined as a LDL-C &lt;70 mg\/dL in participants with ASCVD), compared to 9.3% with placebo. An exploratory endpoint, found that MK-0616 reduced Lipoprotein A by 23.7%. A similar proportion of adverse events occurred in the treatment and placebo group after 16 weeks.<\/p>\n<p>&nbsp;<\/p>\n<p>When discussing the clinical implications of the study at ACC 23, Dr. Ballantyne stated: \u201cwe know LDL is important [and] we know that current injectable PSCK-9 inhibitors are effective [but] have had a poor uptake.\u201d An oral PCSK-9 inhibitor may change that trend.<\/p>\n<p>&nbsp;<\/p>\n<p>This phase 2\u00a0trial successfully demonstrated that an oral, daily, PCSK-9 inhibitor effectively and safely reduced LDL-C. With these encouraging results, clinicians will look forward to a larger phase 3 trial evaluating the effect of MK-0616 on major adverse cardiovascular events.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Key Points\u00a0 -Lowering LDL-C is known to reduce the risk of ASCVD -In patients at very high risk for ASCVD or in those with intolerance to statins, PCSK-9 inhibitors are recommended, however, current PCSK-9 inhibitors are administered subcutaneously, limiting their use -The findings of this Phase 2 trial suggest that MK-0616, an oral PCSK-9 inhibitor [&hellip;]<\/p>\n","protected":false},"author":40603,"featured_media":137923,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[878,8],"tags":[877,45,47,185],"ppma_author":[1029],"class_list":{"0":"post-137922","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-acc-2023","8":"category-news","9":"tag-acc-2023","10":"tag-conference","11":"tag-featured","12":"tag-news","13":"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\/137922","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=137922"}],"version-history":[{"count":1,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/137922\/revisions"}],"predecessor-version":[{"id":137924,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/137922\/revisions\/137924"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/media\/137923"}],"wp:attachment":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=137922"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=137922"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=137922"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=137922"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}