<div class="OutlineElement Ltr SCXW205476133 BCX0"> <p class="Paragraph SCXW205476133 BCX0" xml:lang="EN-US" lang="EN-US" paraid="651104430" paraeid="{c6e27258-479d-4c00-a3f0-84398d986826}{48}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW205476133 BCX0"><span class="NormalTextRun SCXW205476133 BCX0">Noncalcified coronary plaque volume is not<span> </span></span><span class="NormalTextRun SCXW205476133 BCX0">impacted</span><span class="NormalTextRun SCXW205476133 BCX0"><span> </span>by significant triglyceride and remnant cholesterol lowering for 12 months with<span> </span></span><span class="NormalTextRun SpellingErrorV2Themed SCXW205476133 BCX0">olezarsen</span><span class="NormalTextRun SCXW205476133 BCX0"><span> </span>therapy</span><span class="NormalTextRun SCXW205476133 BCX0"><span> </span>in addition to standard lipid lowering therapies</span><span class="NormalTextRun SCXW205476133 BCX0">,</span><span class="NormalTextRun SCXW205476133 BCX0"><span> </span>results from the ESSEN</span><span class="NormalTextRun SCXW205476133 BCX0">C</span><span class="NormalTextRun SCXW205476133 BCX0">E-TIMI trial show.</span></span><span class="EOP Selected SCXW205476133 BCX0" data-ccp-props="{}"> </span></p> </div> <div class="OutlineElement Ltr SCXW205476133 BCX0"> <p class="Paragraph SCXW205476133 BCX0" xml:lang="EN-US" lang="EN-US" paraid="1944270245" paraeid="{e35b3b68-7b41-4600-b064-c696a9abb920}{60}"><span class="NormalTextRun SCXW205476133 BCX0">Data were presented on Monday by Nocholas Marston, MD, MPH, during a late-breaking clinical trials session at the American College of Cardiology (ACC) 2026 Scientific Sessions in New Orleans.</span><span class="EOP Selected SCXW205476133 BCX0" data-ccp-props="{}"> </span></p> </div> <div class="OutlineElement Ltr SCXW205476133 BCX0"> <p class="Paragraph SCXW205476133 BCX0" xml:lang="EN-US" lang="EN-US" paraid="2082979938" paraeid="{9a7e8468-58bd-4338-b3ac-010b09eee6e7}{10}"><span class="NormalTextRun SCXW205476133 BCX0">Data were simultaneously published in<span> </span></span><span class="NormalTextRun SCXW205476133 BCX0">Circulation</span><span class="NormalTextRun SCXW205476133 BCX0">.</span><span class="EOP Selected SCXW205476133 BCX0" data-ccp-props="{}"> </span></p> </div> <div class="OutlineElement Ltr SCXW205476133 BCX0"> <p class="Paragraph SCXW205476133 BCX0" xml:lang="EN-US" lang="EN-US" paraid="1246930921" paraeid="{9426288b-cc9e-4e36-8ca2-af83277e9f6b}{148}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW205476133 BCX0"><span class="NormalTextRun SpellingErrorV2Themed SCXW205476133 BCX0">Olezarsen</span><span class="NormalTextRun SCXW205476133 BCX0"><span> </span>is an antisense oligonucleotide that reduces triglycerides by<span> </span></span><span class="NormalTextRun SCXW205476133 BCX0">roughly 60%</span><span class="NormalTextRun SCXW205476133 BCX0"><span> </span>and remnant cholesterol by<span> </span></span><span class="NormalTextRun SCXW205476133 BCX0">roughly 70%</span><span class="NormalTextRun SCXW205476133 BCX0">. This therapy may<span> </span></span><span class="NormalTextRun SCXW205476133 BCX0">help reduce coronary plaque in patients with moderate hypertriglyceridemia and coronary atherosclerosis.</span></span><span class="EOP Selected SCXW205476133 BCX0" data-ccp-props="{}"> </span></p> </div> <div class="OutlineElement Ltr SCXW205476133 BCX0"> <p class="Paragraph SCXW205476133 BCX0" xml:lang="EN-US" lang="EN-US" paraid="1631659050" paraeid="{757c7e88-6499-4932-9f51-7020c61e8fc0}{181}"><span class="NormalTextRun SCXW205476133 BCX0">Investigators in the<span> </span></span><a class="Hyperlink SCXW205476133 BCX0" href="https://clinicaltrials.gov/study/NCT05610280" target="_blank" rel="noreferrer noopener"><span class="NormalTextRun SCXW205476133 BCX0" data-ccp-charstyle="Hyperlink">ESSENCE-TIMI</span></a><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW205476133 BCX0"><span> </span><span class="NormalTextRun SCXW205476133 BCX0">(A Study of<span> </span></span><span class="NormalTextRun SpellingErrorV2Themed SCXW205476133 BCX0">Olezarsen</span><span class="NormalTextRun SCXW205476133 BCX0"><span> </span>in Participants<span> </span></span><span class="NormalTextRun SCXW205476133 BCX0">With</span><span class="NormalTextRun SCXW205476133 BCX0"><span> </span>Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease, or With Severe Hypertriglyceridemia)<span> </span></span><span class="NormalTextRun SCXW205476133 BCX0">trial</span><span class="NormalTextRun SCXW205476133 BCX0"><span> </span>— a randomized, placebo-controlled trial — examined the use of<span> </span></span><span class="NormalTextRun SpellingErrorV2Themed SCXW205476133 BCX0">olezarsen</span><span class="NormalTextRun SCXW205476133 BCX0"><span> </span>versus placebo in patients with triglycerides greater than<span> </span></span><span class="NormalTextRun SCXW205476133 BCX0">150 mg</span><span class="NormalTextRun SCXW205476133 BCX0">/dL,<span> </span></span><span class="NormalTextRun SCXW205476133 BCX0">high risk</span><span class="NormalTextRun SCXW205476133 BCX0"><span> </span>or</span><span class="NormalTextRun SCXW205476133 BCX0"><span> </span>current cardiovascular disease and non-calcified plaque. Coronary computed tomography angiography (CCTA) was used to evaluate patients at baseline.</span></span><span class="EOP Selected SCXW205476133 BCX0" data-ccp-props="{}"> </span></p> </div> <div class="OutlineElement Ltr SCXW205476133 BCX0"> <p class="Paragraph SCXW205476133 BCX0" xml:lang="EN-US" lang="EN-US" paraid="1849797285" paraeid="{ac196b6d-964c-46e5-abb2-d3725e3e5868}{137}"><span class="NormalTextRun SCXW205476133 BCX0">The percentage change of non-calcified plaque volume (NCVP) from baseline to 12 months was the primary endpoint in this study.</span><span class="EOP Selected SCXW205476133 BCX0" data-ccp-props="{}"> </span></p> </div> <div class="OutlineElement Ltr SCXW205476133 BCX0"> <p class="Paragraph SCXW205476133 BCX0" xml:lang="EN-US" lang="EN-US" paraid="866740618" paraeid="{89441d47-294e-4a4d-ad80-7087f97b34e9}{255}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW205476133 BCX0"><span class="NormalTextRun SCXW205476133 BCX0">A total of 468 participants were included in the study (mean age=63 years, 31% women), and 349 patients received<span> </span></span><span class="NormalTextRun SpellingErrorV2Themed SCXW205476133 BCX0">olezarsen</span><span class="NormalTextRun SCXW205476133 BCX0"><span> </span>and 119 patients received placebo.<span> </span></span></span><span class="EOP Selected SCXW205476133 BCX0" data-ccp-props="{}"> </span></p> </div> <div class="OutlineElement Ltr SCXW205476133 BCX0"> <p class="Paragraph SCXW205476133 BCX0" xml:lang="EN-US" lang="EN-US" paraid="1254873266" paraeid="{e3df29b5-abda-4d43-b253-1749aaf121e5}{219}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW205476133 BCX0"><span class="NormalTextRun SCXW205476133 BCX0">At 6-month follow-up, patients in the<span> </span></span><span class="NormalTextRun SpellingErrorV2Themed SCXW205476133 BCX0">olezarsen</span><span class="NormalTextRun SCXW205476133 BCX0"><span> </span>group had triglycerides reduced by 63.9% and remnant cholesterol reduced by 71.9%.<span> </span></span><span class="NormalTextRun SCXW205476133 BCX0">Low-density lipoprotein cholesterol (LDL-C) levels<span> </span></span><span class="NormalTextRun SCXW205476133 BCX0">remained</span><span class="NormalTextRun SCXW205476133 BCX0"><span> </span>the same. However, at 12-month follow-up,<span> </span></span><span class="NormalTextRun SCXW205476133 BCX0">no differences were seen between<span> </span></span><span class="NormalTextRun SpellingErrorV2Themed SCXW205476133 BCX0">olezarsen</span><span class="NormalTextRun SCXW205476133 BCX0"><span> </span>and placebo patients (p=0.36).</span></span><span class="EOP Selected SCXW205476133 BCX0" data-ccp-props="{}"> </span></p> </div> <div class="OutlineElement Ltr SCXW205476133 BCX0"> <p class="Paragraph SCXW205476133 BCX0" xml:lang="EN-US" lang="EN-US" paraid="160135389" paraeid="{a3e6c718-a7bb-4be8-ba1e-5159c8e0d7c4}{228}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW205476133 BCX0"><span class="NormalTextRun SCXW205476133 BCX0">Additionally, no differences were observed between the two groups with regard to low-attenuation,<span> </span></span><span class="NormalTextRun SCXW205476133 BCX0">calcified</span><span class="NormalTextRun SCXW205476133 BCX0"><span> </span>or total plaque volumes at 1-year follow-up.</span></span><span class="EOP Selected SCXW205476133 BCX0" data-ccp-props="{}"> </span></p> </div> <div class="OutlineElement Ltr SCXW205476133 BCX0"> <p class="Paragraph SCXW205476133 BCX0" xml:lang="EN-US" lang="EN-US" paraid="20962903" paraeid="{1e913a72-31fa-4224-95b1-e9a4eb88e87b}{31}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW205476133 BCX0"><span class="NormalTextRun SCXW205476133 BCX0">“Treatment with<span> </span></span><span class="NormalTextRun SpellingErrorV2Themed SCXW205476133 BCX0">olezarsen</span><span class="NormalTextRun SCXW205476133 BCX0"><span> </span>on top of standard of care lipid-lowering therapy in patients with largely moderate hypertriglyceridemia substantially lowers triglycerides and remnant cholesterol and modestly lowers<span> </span></span><span class="NormalTextRun SCXW205476133 BCX0">ApoB but</span><span class="NormalTextRun SCXW205476133 BCX0"><span> </span>did not affect non-calcified coronary plaque volume at 12 months,” Dr. Marston said in a corresponding ACC press release.</span></span><span class="EOP Selected SCXW205476133 BCX0" data-ccp-props="{}"> </span></p> </div> <div class="OutlineElement Ltr SCXW205476133 BCX0"> <p class="Paragraph SCXW205476133 BCX0" xml:lang="EN-US" lang="EN-US" paraid="72919289" paraeid="{e8372d9b-ece1-4cae-80f1-911075735816}{94}"><span data-contrast="auto" xml:lang="EN-US" lang="EN-US" class="TextRun SCXW205476133 BCX0"><span class="NormalTextRun SCXW205476133 BCX0">“Ultimately, a cardiovascular outcomes trial would need to be performed to determine the cardiovascular benefit of long-term ApoC3 inhibition, tested either as a monotherapy or in combination with another lipid-lowering therapy</span><span class="NormalTextRun SCXW205476133 BCX0">."</span></span><span class="EOP Selected SCXW205476133 BCX0" data-ccp-props="{}"> </span></p> </div> <div class="OutlineElement Ltr SCXW205476133 BCX0"> <p class="Paragraph SCXW205476133 BCX0" xml:lang="EN-US" lang="EN-US" paraid="1191434305" paraeid="{ab06eb39-06e0-46f1-b418-a599cb25589a}{69}"><strong><span class="NormalTextRun SCXW205476133 BCX0">This study was funded by Ionis Pharmaceuticals.</span><span class="EOP Selected SCXW205476133 BCX0" data-ccp-props="{}"> </span></strong></p> </div> <div class="OutlineElement Ltr SCXW205476133 BCX0"> <p class="Paragraph SCXW205476133 BCX0" xml:lang="EN-US" lang="EN-US" paraid="281830413" paraeid="{b0f0e6b7-0621-407b-9a80-39af493b69dc}{104}"><strong><span class="NormalTextRun SCXW205476133 BCX0">Source:</span><span class="EOP Selected SCXW205476133 BCX0" data-ccp-props="{}"> </span></strong></p> </div> <div class="OutlineElement Ltr SCXW205476133 BCX0"> <p class="Paragraph SCXW205476133 BCX0" xml:lang="EN-US" lang="EN-US" paraid="2911075" paraeid="{b0f0e6b7-0621-407b-9a80-39af493b69dc}{168}"><span class="NormalTextRun SCXW205476133 BCX0">Marston NA, Bergmark BA, Prohaska TA, et al. Effect of APO3 inhibition with olezarsen on coronary atherosclerosis: Essence-TIMI 73b study.<span> </span></span><em><span class="NormalTextRun SCXW205476133 BCX0">Circulation</span></em><span class="NormalTextRun SCXW205476133 BCX0">. 2026 March 30 (Article in Press).</span><span class="EOP Selected SCXW205476133 BCX0" data-ccp-props="{}"> </span></p> </div> <div class="OutlineElement Ltr SCXW205476133 BCX0"> <p class="Paragraph SCXW205476133 BCX0" xml:lang="EN-US" lang="EN-US" paraid="1762495738" paraeid="{2810937c-a311-4ebf-b6b9-7e42fd8d64ca}{211}"><strong><span class="NormalTextRun SCXW205476133 BCX0">Image Credit: Screenshot by Bailey G. Salimes, CRTonline.org.</span><span class="EOP Selected SCXW205476133 BCX0" data-ccp-props="{}"> </span></strong></p> </div>