{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:40:28Z","timestamp":1787020828519,"version":"build-2736575974"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T00:00:00Z","timestamp":1609891200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T00:00:00Z","timestamp":1609891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100006396","name":"Alexion Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006396","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      If symptomatic in infants, the autosomal recessive disease lysosomal acid lipase deficiency (LAL-D; sometimes called Wolman disease or LAL-D\/Wolman phenotype) is characterized by complete loss of LAL enzyme activity. This very rare, rapidly progressive form of LAL-D results in severe manifestations leading to failure to thrive and death, usually by 6\u00a0months of age. We report results from 2 open-label studies of enzyme replacement therapy with sebelipase alfa, a recombinant human LAL, in infants with LAL-D: the phase 2\/3 Sur\n                      <jats:underline>v<\/jats:underline>\n                      ival of LAL-D\n                      <jats:underline>I<\/jats:underline>\n                      nfants\n                      <jats:underline>T<\/jats:underline>\n                      reated With Sebelipase\n                      <jats:underline>Al<\/jats:underline>\n                      fa (VITAL) study (NCT01371825) and a phase 2 dose-escalation study (LAL-CL08 [CL08]; NCT02193867). In both, infants received once-weekly intravenous infusions of sebelipase alfa.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The analysis population contained 19 patients (9 in VITAL; 10 in CL08). Kaplan\u2013Meier estimates of survival to 12\u00a0months and 5\u00a0years of age were 79% and 68%, respectively, in the combined population, and the median age of surviving patients was 5.2\u00a0years in VITAL and 3.2\u00a0years in CL08. In both studies, median weight-for-age, length-for-age, and mid-upper arm circumference-for-age\n                      <jats:italic>z<\/jats:italic>\n                      scores increased from baseline to end of study. Decreases in median liver and spleen volume over time were noted in both studies. Short-term transfusion-free hemoglobin normalization was achieved by 100% of patients eligible for assessment in VITAL, in an estimated median (95% confidence interval [CI]) time of 4.6 (0.3\u201316.6) months. In CL08, short-term transfusion-free hemoglobin normalization was achieved by 70% of patients eligible for assessment, in an estimated median (95% CI) time of 5.5 (3.7\u201319.6) months. No patient discontinued treatment because of treatment-emergent adverse events. Most infusion-associated reactions (94% in VITAL and 88% in CL08) were mild or moderate in severity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The findings of these 2 studies of infants with rapidly progressive LAL-D demonstrated that enzyme replacement therapy with sebelipase alfa prolonged survival with normal psychomotor development, improved growth, hematologic\u00a0parameters, and liver parameters, and was generally well tolerated, with an acceptable safety profile.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-020-01577-4","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T14:04:06Z","timestamp":1609941846000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Long-term survival with sebelipase alfa enzyme replacement therapy in infants with rapidly progressive lysosomal acid lipase deficiency: final results from 2 open-label studies"],"prefix":"10.1186","volume":"16","author":[{"given":"Suresh","family":"Vijay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anais","family":"Brassier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arunabha","family":"Ghosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Fecarotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Abel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachin","family":"Marulkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon A.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,6]]},"reference":[{"key":"1577_CR1","volume-title":"The Online Metabolic and Molecular Bases of Inherited Disease","author":"GA Grabowski","year":"2019","unstructured":"Grabowski GA, Valayannopoulos V, Goodman ZD, Balwani M, et al. Lysosomal acid lipase deficiency: the continuous spectra of disease variants. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, et al., editors. The Online Metabolic and Molecular Bases of Inherited Disease. New York: McGraw-Hill; 2019."},{"issue":"11","key":"1577_CR2","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1056\/NEJMoa1501365","volume":"373","author":"B Burton","year":"2015","unstructured":"Burton B, Balwani M, Feillet F, Baric I, Burrow T, Camarena Grande C, et al. A phase 3 trial of sebelipase alfa in lysosomal acid lipase deficiency. N Engl J Med. 2015;373(11):1010\u201320.","journal-title":"N Engl J Med"},{"issue":"1","key":"1577_CR3","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.atherosclerosis.2014.04.003","volume":"235","author":"Z Reiner","year":"2014","unstructured":"Reiner Z, Guardamagna O, Nair D, Soran H, Hovingh K, Bertolini S, et al. 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The protocols, amendments, and informed consent forms were approved by an institutional review board or independent ethics committee prior to initiation of the study at each study site. The patients\u2019 parent\/legal guardian(s) provided written informed consent.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"S. Vijay, A. Ghosh, and S. Fecarotta have received consultancy fees\/honoraria from Alexion Pharmaceuticals, Inc. F. Abel and S. Marulkar are employees of and may own stock\/stock options in Alexion Pharmaceuticals, Inc. which sponsored the studies. A. Brassier has received fees and travel support for conferences from Alexion Pharmaceuticals, Inc. S. A. Jones has received consultancy fees, grants, and travel support for conferences from Alexion Pharmaceuticals, Inc.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"13"}}