Abstract:
BACKGROUND:Gaucher Disease type 1 (GD1) often manifests in childhood. Early treatment with enzyme replacement therapy (ERT) may prevent disease complications. We report the assessment of velaglucerase alfa ERT in pediatric GD1 patients who participated in a long-term extension study (HGT-GCB-044, ClinicalTrials.gov Identifier NCT00635427). METHODS:Safety and efficacy were evaluated in pediatric patients receiving velaglucerase alfa 30-60U/kg by intravenous infusion every other week. In addition to key hematological and visceral efficacy assessments, exploratory assessments conducted specifically in pediatric patients included evaluation of height, bone age, bone marrow burden, and Tanner stage of puberty. RESULTS:The study included 24 pediatric patients. Fifteen patients were naïve to ERT on entry into the preceding trials TKT032 (12-month trial) or HGT-GCB-039 (9-month trial): in the preceding trials, ten of these 15 patients received velaglucerase alfa and five patients received imiglucerase ERT. Nine patients in the study were previously treated with imiglucerase for >30months and were switched to velaglucerase alfa in the preceding trial TKT034 (12-month trial). Cumulative ERT exposure in the clinical studies ranged from 2.0 to 5.8years. Three serious adverse events, including a fatal convulsion, were reported; none were deemed related to velaglucerase alfa. One patient tested positive for anti-velaglucerase alfa antibodies. An efficacy assessment at 24months showed that velaglucerase alfa had positive effects on primary hematological and visceral parameters in treatment-naïve patients, which were maintained with longer-term treatment. Disease parameters were stable in patients switched from long-term imiglucerase ERT. Exploratory results may suggest benefits of early treatment to enable normal growth in pediatric patients. CONCLUSION:The safety profile and clinical response seen in pediatric patients are consistent with results reported in adults.
journal_name
Mol Genet Metabjournal_title
Molecular genetics and metabolismauthors
Smith L,Rhead W,Charrow J,Shankar SP,Bavdekar A,Longo N,Mardach R,Harmatz P,Hangartner T,Lee HM,Crombez E,Pastores GMdoi
10.1016/j.ymgme.2015.05.012subject
Has Abstractpub_date
2016-02-01 00:00:00pages
164-71issue
2eissn
1096-7192issn
1096-7206pii
S1096-7192(15)30017-2journal_volume
117pub_type
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journal_title:Molecular genetics and metabolism
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pub_type: 杂志文章
doi:10.1006/mgme.2000.3105
更新日期:2001-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.ymgme.2015.11.004
更新日期:2016-02-01 00:00:00
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