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ALZ\u2010801\/valiltramiprosate, an oral brain\u2010penetrant amyloid beta oligomer inhibitor is being evaluated in\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54\/\u03b54 homozygotes with early AD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>This Phase 3 randomized, double\u2010blind, placebo\u2010controlled, 78\u2010week study of ALZ\u2010801 administered as 265\u00a0mg twice per day tablets, enrolled 50\u2010 to 80\u2010year\u2010old homozygotes with Mini\u2010Mental State Examination (MMSE) \u2265 22 and Clinical Dementia Rating\u2013Global Score 0.5 or 1.0. The study is powered to detect a 2.0 to 2.5 drug\u2013placebo difference on the Alzheimer's Disease Assessment Scale 13\u2010item Cognitive subscale primary outcome with 150 subjects\/arm. The key secondary outcomes are Clinical Dementia Rating\u2013Sum of Boxes and Instrumental Activities of Daily Living; volumetric magnetic resonance imaging and fluid biomarkers are additional outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>The APOLLOE4 Phase 3 trial enrolled 325 subjects with a mean age of 69 years, 51% female, MMSE 25.6, and 65% mild cognitive impairment. Topline results are expected in 2024.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      APOLLOE4 is the first disease\u2010modification AD trial focused on\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54\/\u03b54 homozygotes. Oral ALZ\u2010801 has the potential to be the first effective and safe anti\u2010amyloid treatment for the high\u2010risk\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54\/\u03b54 population.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            The APOLLOE4 Phase 3, placebo\u2010controlled, 78\u2010week study is designed to evaluate the efficacy and safety of ALZ\u2010801 265\u00a0mg twice per day in early Alzheimer's disease (AD) subjects with the apolipoprotein E (\n                            <jats:italic>APOE<\/jats:italic>\n                            ) \u03b54\/\u03b54 genotype.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            The enrolled early AD population (\n                            <jats:italic>N<\/jats:italic>\n                            \u00a0=\u00a0325) has 51% females, a mean age = 69 years, and a mean Mini\u2010Mental State Examination = 25.6, with the majority being mild cognitive impairment subjects, a similar disease stage to the lecanemab Phase 3 AD trial (Clarity AD).\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The primary outcome is the cognitive Alzheimer's Disease Assessment Scale 13\u2010item Cognitive subscale, with two functional measures as key secondary outcomes (Clinical Dementia Rating\u2013Sum of Boxes, Amsterdam\u2010Instrumental Activities of Daily Living), and with hippocampal volume and fluid biomarkers as additional outcomes.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The study is unique in allowing a large number of microhemorrhages or siderosis at baseline magnetic resonance imaging, lesions that indicate concomitant cerebral amyloid angiopathy (CAA).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>At baseline, 32% of the enrolled population had at least 1 microhemorrhage, 24% had 1 to 4, and 8% had &gt; 4 microhemorrhages; 10% had at least 1 siderosis lesion; with more males than females having microhemorrhages (63% vs. 37%) and siderosis (68% vs. 32%).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Study results will become available in the second half of 2024 and, if positive, ALZ\u2010801 may become the first oral drug to demonstrate a favorable benefit\/risk profile in\n                            <jats:italic>APOE<\/jats:italic>\n                            \u03b54\/\u03b54 AD subjects.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.12498","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T02:19:45Z","timestamp":1723601985000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["APOLLOE4 Phase 3 study of oral ALZ\u2010801\/valiltramiprosate in\n                    <i>APOE<\/i>\n                    \u03b54\/\u03b54 homozygotes with early Alzheimer's disease: Trial design and baseline characteristics"],"prefix":"10.1002","volume":"10","author":[{"given":"Susan","family":"Abushakra","sequence":"first","affiliation":[{"name":"Alzheon, Inc.  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