{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T08:18:58Z","timestamp":1778055538096,"version":"3.51.4"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This exploratory analysis of the NEURO\u2010TTRansform Phase 3 trial evaluated the efficacy of eplontersen in patients with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy by genetic variant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Changes from baseline in NEURO\u2010TTRansform primary endpoints serum transthyretin (TTR) at Week 65, modified Neuropathy Impairment Score+7 (mNIS+7) composite score, and Norfolk Quality of Life\u2010Diabetic Neuropathy (Norfolk QoL\u2010DN) total score at Week 66 were evaluated in patients with early\u2010onset (aged &lt;\u200950\u2009years) and late\u2010onset (aged \u2265\u200950\u2009years) Val30Met (p.Val50Met) or non\u2010Val30Met ATTRv amyloidosis with polyneuropathy. Secondary endpoints from NEURO\u2010TTRansform were also evaluated by genetic variant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In total, 144 patients with early\u2010onset (\n                      <jats:italic>n\u2009=<\/jats:italic>\n                      \u200954) or late\u2010onset (\n                      <jats:italic>n\u2009=<\/jats:italic>\n                      \u200931) Val30Met or non\u2010Val30Met (\n                      <jats:italic>n\u2009=<\/jats:italic>\n                      \u200959), ATTRv amyloidosis with polyneuropathy were randomized to eplontersen. A further 60 patients from NEURO\u2010TTR with early\u2010onset (\n                      <jats:italic>n\u2009=<\/jats:italic>\n                      \u200916) or late\u2010onset (\n                      <jats:italic>n\u2009=<\/jats:italic>\n                      \u200917) Val30Met or non\u2010Val30Met (\n                      <jats:italic>n\u2009=<\/jats:italic>\n                      \u200927), served as a historical placebo group. The mean percentage difference (95% confidence interval) in serum TTR was \u221279.9 (\u221287.8, \u221272.0), \u221285.0 (\u221293.3, \u221276.6), and \u221270.6 (\u221277.7, \u221263.5) with eplontersen versus placebo in the early\u2010 and late\u2010onset Val30Met, and non\u2010Val30Met groups, respectively. Across subgroups, the change from baseline to Week 66 in mNIS+7 composite score was generally well maintained, and the Norfolk QoL\u2010DN total score improved with eplontersen versus worsening with placebo. The Polyneuropathy Disability score was maintained in most patients. From baseline to Week 65, the modified body mass index was maintained with eplontersen compared to a marked reduction (worsening) for placebo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Findings were suggestive of consistent benefits in reducing neuropathy impairment and improving QoL with eplontersen versus historical placebo, across\n                      <jats:italic>TTR<\/jats:italic>\n                      variants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov: NCT04136184, NCT01737398<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70580","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T06:25:56Z","timestamp":1774938356000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of Eplontersen in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy Across Genetic Variants: An Exploratory Analysis From the\n                    <scp>NEURO<\/scp>\n                    \u2010\n                    <scp>TTRansform<\/scp>\n                    Trial"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6174-9232","authenticated-orcid":false,"given":"Julian D.","family":"Gillmore","sequence":"first","affiliation":[{"name":"National Amyloidosis Centre University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8722-4108","authenticated-orcid":false,"given":"David","family":"Adams","sequence":"additional","affiliation":[{"name":"Neurology Department, CHU de Bic\u00eatre, AP\u2010HP Universit\u00e9 Paris\u2010Saclay  Le\u2010Kremlin\u2010Bic\u00eatre France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8942-7662","authenticated-orcid":false,"given":"Markus","family":"Weiler","sequence":"additional","affiliation":[{"name":"Amyloidosis Center and Department of Neurology Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmad","family":"Masri","sequence":"additional","affiliation":[{"name":"Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Obici","sequence":"additional","affiliation":[{"name":"Amyloidosis Research and Treatment Centre IRCCS Fondazione Policlinico San Matteo  Pavia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonatan","family":"N\u00e5tman","sequence":"additional","affiliation":[{"name":"BioPharmaceuticals Business Unit AstraZeneca  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. 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