{"id":138749,"date":"2025-04-01T09:36:42","date_gmt":"2025-04-01T13:36:42","guid":{"rendered":"https:\/\/cardiologynownews.org\/?p=138749"},"modified":"2026-01-28T19:26:13","modified_gmt":"2026-01-29T00:26:13","slug":"pursuit-trial-dose-dependent-reduction-in-ldl-c-with-azd0780-oral-pcsk9-inhibitor","status":"publish","type":"post","link":"https:\/\/cardiologynownews.org\/?p=138749","title":{"rendered":"PURSUIT Trial \u2013 Dose Dependent Reduction in LDL-C with AZD0780, Oral PCSK9 inhibitor"},"content":{"rendered":"<p><span style=\"font-weight: 400;\">Key Points<\/span><\/p>\n<ul>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">The majority of ASCVD patients fail to achieve guideline endorsed LDL targets\u00a0<\/span><\/li>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">The PURSUIT trial randomized 428 patients in a 1:1:1:1 ratio to receive oral AZD0780 1, 3, 10, or 30mg, or matching placebo for 12 weeks.\u00a0<\/span><\/li>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">AZD0780 demonstrated robust, dose-dependent reductions in LDL-C with a favorable safety and tolerability profile supporting further development of this once daily, oral treatment.\u00a0<\/span><\/li>\n<\/ul>\n<p><!--more--><\/p>\n<p><span style=\"font-weight: 400;\">Despite the availability of several lipid-lowering therapies, only 1 in 3 patients with ASCVD achieve an LDL-C target of &lt; 70 mg\/dL after 2 years. Currently FDA-approved PCSK9 inhibitors reduce LDL-C by 50% or more but require subcutaneous injection which can be a barrier for some patients who prefer taking medications by oral administration. AZD0780, is an oral, small molecule, PCSK9 inhibitor which prevents lysosomal trafficking and LDL receptor degradation.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400;\">The PURSUIT trial was a phase 2 randomized, multicenter, placebo controlled, dose-ranging phase II trial conducted in 55 international sites undertaken to assess the efficacy and safety of AZD0780 in patients with hypercholesteremia. The trial enrolled patients with an LDL-C \u2265 70 mg\/dL and &lt; 190 mg\/dL and triglycerides &lt; 400 mg\/dL. Participants were required to be on a stable dose of moderate or high-intensity statin. The trial excluded individuals with an estimated glomerular filtration rate &lt; 45 mL\/min\/1.73 m<\/span><span style=\"font-weight: 400;\">2<\/span><span style=\"font-weight: 400;\">, an acute ischemic cardiovascular event within 12 months of randomization, and poorly controlled type 2 diabetes mellitus with a hemoglobin A<\/span><span style=\"font-weight: 400;\">1c<\/span><span style=\"font-weight: 400;\"> &gt; 10%.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400;\">In total, the study randomized 428 patients, of whom 426 started treatment. Patients were 52.1% male, with an average age of 62.4, and the mean LDL-C levels at baseline was 100.7.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400;\">For the primary endpoint, AZD0780 significantly reduced LDL-C levels compared to placebo at 12 weeks in a dose-dependent manner. Placebo adjusted LDL-C reductions at 12-weeks were 35.3% for the AZD0780 1 mg group, 37.9% for the AZD0780 3 mg group, 45.2% for the AZD0780 10 mg group, and 50.7% for the AZD0780 30 mg group. In the highest dose group, AZD0780 30 mg, 84.2% achieved an LDL-C target of &lt;70 mg\/dL. Adverse events were similar between the entire AZD0780 treatment group (38.2%) as compared to placebo (32.6%).<\/span><\/p>\n<p><span style=\"font-weight: 400;\">In conclusion, AZD0780 demonstrated robust, dose-dependent, reductions in LDL-C of up to 50.7% from baseline to 12 weeks. The investigators commented that \u201cAs a highly-effective and well tolerated once-daily oral therapy, AZD0780 could become part of a simplified treatment strategy to help more patients quickly and reliably achieve ACC\/AHA guideline LDL-C recommendations.\u201d<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Key Points The majority of ASCVD patients fail to achieve guideline endorsed LDL targets\u00a0 The PURSUIT trial randomized 428 patients in a 1:1:1:1 ratio to receive oral AZD0780 1, 3, 10, or 30mg, or matching placebo for 12 weeks.\u00a0 AZD0780 demonstrated robust, dose-dependent reductions in LDL-C with a favorable safety and tolerability profile supporting further [&hellip;]<\/p>\n","protected":false},"author":40624,"featured_media":138226,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[898,8],"tags":[899,47,185],"ppma_author":[1080],"class_list":{"0":"post-138749","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-acc-2025","8":"category-news","9":"tag-acc-2025","10":"tag-featured","11":"tag-news","12":"author-inbar-mccarthy-md"},"authors":[{"term_id":1080,"user_id":40624,"is_guest":0,"slug":"inbar-mccarthy-md","display_name":"Inbar McCarthy MD","avatar_url":"https:\/\/secure.gravatar.com\/avatar\/?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\/138749","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\/40624"}],"replies":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=138749"}],"version-history":[{"count":1,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/138749\/revisions"}],"predecessor-version":[{"id":138750,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/138749\/revisions\/138750"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/media\/138226"}],"wp:attachment":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=138749"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=138749"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=138749"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=138749"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}