Amarin Corp Plc (AMRN)

[rosemountbomber]

For anyone wanting to read the full description:

"LP019- THE BRAIN AMYLOID AND VASCULAR EFFECTS OF EICOSAPENTAENOIC ACID (BRAVE) STUDY. C. Van Hulle1, H. Zylstra1, K. Cronin1, A. Cole1, E. Beckman1, A. Eierman2, M. Blazel3, K. Lazar1, K. Johnson1, L. Rivera1, C. Gleason1, H. Zetterberg4, S. Johnson1, C. Carlsson1 (1. University of Wisconsin-Madison - Madison (United States), 2. Medical College of Wisconsin-Green Bay - Green By (United States), 3. Case Western Reserve University School of Medicine - Cleveland Ohio (United States), 4. Sahlgrenska Academy - Moldal (Sweden))
Background: Alzheimer’s disease (AD) pathology is characterized by amyloid plaques, neurofibrillary tangles, and reduced regional cerebral blood flow (rCBF) in brain regions related to memory and learning. The omega-3 fatty acid eicosapentaenoic acid (EP A) has beneficial cardioprotective properties, reducing inflammation and enhancing endothelial function. Icosapent ethyl (IPE), a purified form of EPA, improves cardiovascular outcomes and strokes in at-risk patients (NCT01492361). EP A lowers triglycerides without raising LDL, unlike docosahexaenoic acid (DHA)- based omega-3 formulations. Veterans report higher rates of some cardiovascular diseases (CVD) than non-veterans. Given Veterans higher risk for vascular dysfunction, and the high co-occurrence of cerebrovascular dysfunction with AD pathology, improved vascular health may be a key modifiable risk factor for delaying the onset of AD among Veterans. Yet, Veterans remain an understudied population in AD related clinical research. We conducted a proof-of-concept investigation into the efficacy of an FDA approved high dose EPA in improving cerebrovascular function in healthy, cognitively unimpaired Veterans. Methods: Veterans Affairs (VA) eligible Veterans were invited to enroll into an 18-month randomized, placebo-controlled, double-blind, parallel-group clinical trial assessing the efficacy of Vascepa® IPE. The primary outcome is change over baseline in 18-month rCBF on treatment compared to placebo. Secondary outcomes are change over baseline in 18-month CSF biomarkers for AD pathology (Aß42, pTau181, total tau). An exploratory aim is to investigate change in global cognition. At baseline, 9 and 18 months, participants had an MRI scan, LP procedure, and completed the Alzheimer’s Disease Cooperative Study Preclinical Alzheimer’s Cognitive Composite (ADCS-PACC) battery to measure global cognition. To characterize the vascular health of study enrollees, we measured baseline cardiovascular risk factors (atherosclerotic cardiovascular disease [ASCVD] risk score, body mass index, waist-hip ratio, blood pressure, and heart rate). Participants reported on their medication use, health conditions, dietary intake of fish oil, physical and mental activities. We also captured experiences unique to Veterans including military experience, TBI exposure, and PTSD symptoms. Results: We screened 206 individuals for exclusion criteria (memory disorder, inability to complete study protocols); 179 were consented and 131 were randomly assigned in a 1:1 ratio to either placebo or 4mg/day IPE. We have previously presented baseline demographics including military experience, self- reported health, and the baseline associations between cognitive performance and hippocampal volume, cardiovascular risk, and neighborhood disadvantage. Trial outcomes will be completed in Sept 2023. Here we report on mean baseline values for the pre-specified outcomes. At baseline, N=127, 119, and 129 participants had an MRI scan, LP procedure, and complete cognitive battery, respectively (N=111 participants had both successful baseline MRI and LP); to date, 110 participants completed all study visits. Mean global rCBF = 50.2 mL/100g
S93
All abstracts are embargoed until the day and time of presentation at the CTAD Conference
tissue/min (SD=16.2); mean CSF values for Ab42 = 1296 pg/ mL (SD=581), phospho-tau181 = 19.7 pg/mL (SD=6.67), total tau=223 pg/mL (SD=71.8); mean global cognition as measured by the ADCS-PACC = -0.0001 (SD=0.64), suggesting normal amyloid and tau levels and cognitive performance at study entry. Conclusion: The impact of IPE on cerebrovascular health in cognitively unimpaired Veterans will be presented at the conference. Key words: Veterans, omega-3-fatty acid, cerebral blood flow, cerebrospinal fluid. Clinical Trial Registry: NCT02719327; https://clinicaltrials.gov . Disclosures: The authors have nothing to disclose."