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We report 2-year cumulative safety and efficacy data after olipudase alfa treatment in 20 children (four adolescents [12\u201317\u00a0year], nine children [6\u201311\u00a0year], and seven infants\/early child [1\u20135\u00a0year]) with baseline splenomegaly and growth deficits who completed the 1-year ASCEND-Peds clinical trial (NCT02292654) and who continue to receive olipudase alfa in a long-term study (NCT02004704). Efficacy endpoints include spleen and liver volumes, diffusing capacity of the lung for carbon monoxide (DL<jats:sub>CO<\/jats:sub>), high-resolution computed tomography (HRCT) lung imaging, lipid profiles, liver function tests, and height Z-scores.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>All 20 former ASCEND-Peds patients completed at least 2\u00a0years of olipudase alfa treatment. No patient discontinued and no new safety issue arose during the second year of treatment; 99% of adverse events were mild or moderate. During year 2, one patient had two treatment-related serious events of hypersensitivity that resolved. Mean reductions from baseline in spleen and liver volumes were 61% and 49%, respectively (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) and mean percent-predicted-DL<jats:sub>CO<\/jats:sub> increased by 46.6% (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) in nine patients who performed the test at baseline. Lipid profiles and elevated liver transaminase levels that improved or normalized by 1\u00a0year remained stable. Mean height Z-scores improved in all age groups (mean change from baseline 1.17, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Olipudase alfa was generally well-tolerated during 2\u00a0years of treatment. Improvements in clinically relevant disease endpoints observed during the first year of treatment were maintained or augmented in the second year.<\/jats:p>\n                <jats:p><jats:italic>Trial registration<\/jats:italic> NCT02004704 registered 26 Nov 2013, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/record\/NCT02004704\">https:\/\/clinicaltrials.gov\/ct2\/show\/record\/NCT02004704<\/jats:ext-link>.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-022-02587-0","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T11:03:04Z","timestamp":1671015784000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Long-term safety and clinical outcomes of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency: two-year results"],"prefix":"10.1186","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5688-9062","authenticated-orcid":false,"given":"George A.","family":"Diaz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Giugliani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Guffon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon A.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugen","family":"Mengel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Scarpa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Witters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhimanyu","family":"Yarramaneni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole M.","family":"Armstrong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Ortemann-Renon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"issue":"1\u20132","key":"2587_CR1","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.ymgme.2016.12.008","volume":"120","author":"EH Schuchman","year":"2017","unstructured":"Schuchman EH, Desnick RJ. 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All clinical data were de-identified. The study adhered to the principles set out in the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"GAD, SAJ, MS, K. EM, RG, PW, and NG are principal investigators in Sanofi sponsored trials. GAD and SAJ have received honoraria and consulting fees from Sanofi. EM has received research support, honoraria, and consulting fees from Sanofi. RG has received honoraria, consulting fees, speaker fees and travel reimbursement from Sanofi. NG has received honoraria and travel reimbursement from Sanofi. MS has received honoraria, consulting fees, speaker fees and travel reimbursement from Sanofi. PW has participated in advisory boards and received travel reimbursement from Sanofi. AY, JL, NA, YK, CO-R, and MK are employed by Sanofi and may own Sanofi stock.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"437"}}