{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:28:52Z","timestamp":1790202532504,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Acid sphingomyelinase deficiency (ASMD) is a rare debilitating lysosomal storage disease resulting in multisystemic disease manifestations, significant disease burden, and early mortality for some individuals. Enzyme replacement therapy (ERT) with olipudase alfa (Xenpozyme) is the first disease\u2010specific treatment indicated for noncentral nervous system manifestations of ASMD in children and adults. During the 1\u2010year primary analysis of the ASCEND placebo\u2010controlled trial in 36 adults with ASMD, olipudase alfa treatment reduced sphingomyelin storage and was associated with clinically significant improvements relative to placebo in multiple endpoints. An open\u2010label extension of the ASCEND trial followed 35 of 36 adults during olipudase alfa treatment for up to 5\u2009years. Mean time on olipudase alfa was 4.2\u2009\u00b1\u20091.0\u2009years; mean compliance was 90%\u2009\u00b1\u200913%. During long\u2010term olipudase alfa treatment, percent predicted diffusing capacity for carbon monoxide (DL\n                    <jats:sub>CO<\/jats:sub>\n                    ) increased (mean 50.1%\u2009\u00b1\u200910.8% at baseline vs. 66.5%\u2009\u00b1\u200913.3% at final assessment; mean change from baseline of 35.9%\u2009\u00b1\u200927.5% (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). Mean baseline spleen volume of 11.5\u2009\u00b1\u20094.6 multiples of normal (MN) decreased to 4.8\u2009\u00b1\u20092.1 MN at final assessment, mean change from baseline \u221257.5%\u2009\u00b1\u200910.1% (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001) and mean baseline liver volume (1.5\u2009\u00b1\u20090.4\u2009MN) decreased to 0.95\u2009\u00b1\u20090.23\u2009MN at final assessment, (mean change from baseline \u221236.8%\u2009\u00b1\u200911.5%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). Plasma lyso\u2010sphingomyelin levels decreased by 72% from baseline to final assessment. Overall, improvements in clinical parameters occurred regardless of baseline severity. No new safety issues emerged during the trial extension and 98% of treatment emergent adverse events were mild\/moderate. Improvements in visceral ASMD disease with olipudase alfa treatment will significantly impact the disease burden for those with this progressive multiorgan disorder.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70192","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:19:09Z","timestamp":1777371549000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Adults With Acid Sphingomyelinase Deficiency Have Sustained Improvements in Clinical Outcomes With up to 5\u2009Years of Olipudase Alfa Enzyme Replacement Therapy:\n                    <scp>ASCEND<\/scp>\n                    Trial Final Results"],"prefix":"10.1002","volume":"49","author":[{"given":"Melissa P.","family":"Wasserstein","sequence":"first","affiliation":[{"name":"Children's Hospital at Montefiore Albert Einstein College of Medicine  Bronx New York 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