{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T02:58:19Z","timestamp":1761101899510},"reference-count":10,"publisher":"American Society of Hematology","issue":"23","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,6,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Enzyme replacement therapy is the standard of care for symptomatic Gaucher disease. Velaglucerase alfa is a human \u03b2-glucocerebrosidase produced in a well-characterized human cell line. A 9-month phase 1\/2 open-label, single-center trial and ongoing extension study were conducted to evaluate safety and efficacy of velaglucerase alfa. Twelve symptomatic adult type 1 Gaucher patients (intact spleens) received velaglucerase alfa (60 U\/kg per infusion) during phase 1\/2. An extension study was offered to patients completing the trial; step-wise dose reduction (to 30 U\/kg per infusion) was instituted. Eleven patients completed phase 1\/2; 10 entered the extension; 9 patients reached 39 months of extension. No drug-related serious adverse events or withdrawals, and no antibodies were observed. Home therapy was successfully implemented during the extension. Statistically significant improvements (P &lt; .004) were noted in mean percentage change from baseline to 9 months and baseline to 48 months for hemoglobin (+19.2%, +21.7%, respectively), platelet counts (+67.6%, +157.8%, respectively), normalized liver volume (\u221218.2%, \u221242.8%, respectively), and normalized spleen volume (\u221249.5%, \u221279.3%, respectively). These significant clinical changes and safety profile led to phase 3 trials and highlight the potential of velaglucerase alfa as alternative therapy for type 1 Gaucher disease. The extension trial is registered at http:\/\/www.clinicaltrials.gov as NCT00391625.<\/jats:p>","DOI":"10.1182\/blood-2010-02-268649","type":"journal-article","created":{"date-parts":[[2010,3,19]],"date-time":"2010-03-19T02:24:50Z","timestamp":1268965490000},"page":"4651-4656","update-policy":"http:\/\/dx.doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":108,"title":["Phase 1\/2 and extension study of velaglucerase alfa replacement therapy in adults with type 1 Gaucher disease: 48-month experience"],"prefix":"10.1182","volume":"115","author":[{"given":"Ari","family":"Zimran","sequence":"first","affiliation":[{"name":"Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel; and"}]},{"given":"Gheona","family":"Altarescu","sequence":"additional","affiliation":[{"name":"Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel; and"}]},{"given":"Mici","family":"Philips","sequence":"additional","affiliation":[{"name":"Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel; and"}]},{"given":"Drorit","family":"Attias","sequence":"additional","affiliation":[{"name":"Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel; and"}]},{"given":"Marina","family":"Jmoudiak","sequence":"additional","affiliation":[{"name":"Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel; and"}]},{"given":"Maher","family":"Deeb","sequence":"additional","affiliation":[{"name":"Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel; and"}]},{"given":"Nan","family":"Wang","sequence":"additional","affiliation":[{"name":"Shire Human Genetic Therapies Inc, Cambridge, MA"}]},{"given":"Kiran","family":"Bhirangi","sequence":"additional","affiliation":[{"name":"Shire Human Genetic Therapies Inc, Cambridge, MA"}]},{"given":"Gabriel M.","family":"Cohn","sequence":"additional","affiliation":[{"name":"Shire Human Genetic Therapies Inc, Cambridge, MA"}]},{"given":"Deborah","family":"Elstein","sequence":"additional","affiliation":[{"name":"Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel; and"}]}],"member":"234","reference":[{"issue":"21","key":"2019111723384903500_B1","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1056\/NEJM199105233242104","article-title":"Replacement therapy for inherited enzyme deficiency\u2013macrophage-targeted glucocerebrosidase for Gaucher's disease.","volume":"324","author":"Barton","year":"1991","journal-title":"N Engl J Med"},{"issue":"1","key":"2019111723384903500_B2","doi-asserted-by":"crossref","first-page":"33","DOI":"10.7326\/0003-4819-122-1-199501010-00005","article-title":"Enzyme therapy in type 1 Gaucher disease: comparative efficacy of mannose-terminated glucocerebrosidase from natural and recombinant sources.","volume":"122","author":"Grabowski","year":"1995","journal-title":"Ann Intern Med"},{"issue":"8963","key":"2019111723384903500_B3","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1016\/S0140-6736(95)91038-7","article-title":"Replacement therapy with imiglucerase for type 1 Gaucher's disease.","volume":"345","author":"Zimran","year":"1995","journal-title":"Lancet"},{"issue":"1","key":"2019111723384903500_B4","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.bcmd.2007.02.008","article-title":"A pharmacokinetic analysis of a novel enzyme replacement therapy with Gene-Activated human glucecerebrosidase (GA-GCB) in patients with type 1 Gaucher disease.","volume":"39","author":"Zimran","year":"2007","journal-title":"Blood Cells Mol Dis"},{"key":"2019111723384903500_B5","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1053\/j.seminhematol.2004.07.009","article-title":"Therapeutic goals in the treatment of Gaucher disease.","volume":"41","author":"Pastores","year":"2004","journal-title":"Semin Hematol"},{"issue":"2","key":"2019111723384903500_B6","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1097\/01.GIM.0000153660.88672.3C","article-title":"Individualization of long-term enzyme replacement therapy for Gaucher disease.","volume":"7","author":"Andersson","year":"2005","journal-title":"Genet Med"},{"issue":"1\u20132","key":"2019111723384903500_B7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jim.2004.06.002","article-title":"Recommendations for the design and optimization of immunoassays used in the detection of host antibodies against biotechnology products.","volume":"289","author":"Mire-Sluis","year":"2004","journal-title":"J Immunol Methods"},{"issue":"2","key":"2019111723384903500_B8","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.ymgme.2006.09.003","article-title":"The long term international safety experience of imiglucerase therapy for Gaucher disease.","volume":"90","author":"Starzyk","year":"2007","journal-title":"Molec Genet Metab"},{"key":"2019111723384903500_B9","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1056\/NEJMp0906922","article-title":"Drug shortages and public health.","volume":"361","author":"Steinbrook","year":"2009","journal-title":"N Engl J Med"},{"issue":"12","key":"2019111723384903500_B10","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1002\/ajh.21280","article-title":"A benchmark analysis of the achievement of therapeutic goals for type 1 Gaucher disease patients treated with imiglucerase.","volume":"83","author":"Weinreb","year":"2008","journal-title":"Am J Hematol"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/115\/23\/4651\/1327083\/zh802310004651.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/115\/23\/4651\/1327083\/zh802310004651.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T04:38:57Z","timestamp":1574051937000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/115\/23\/4651\/27738\/Phase-12-and-extension-study-of-velaglucerase-alfa"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,6,10]]},"references-count":10,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2010,6,10]]}},"URL":"https:\/\/doi.org\/10.1182\/blood-2010-02-268649","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,6,10]]}}}