title: Long-term velaglucerase alfa treatment in children with Gaucher disease type 1 naïve to enzyme replacement therapy or previously treated with imiglucerase.
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.
  
  
  CONCLUSIONS
  The safety profile and clinical response seen in pediatric patients are consistent with results reported in adults.
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy-Kansas City, 2401 Gillham Road, Kansas City, MO 64108, USA. Electronic address: ldsmith@cmh.edu.
authors.forename: Laurie
authors.initials: L
authors.lastname: Smith
authors.affiliation: Children's Hospital of Wisconsin, Milwaukee, WI, USA.
authors.forename: William
authors.initials: W
authors.lastname: Rhead
authors.affiliation: Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Charrow
authors.affiliation: Department of Human Genetics, Division of Medical Genetics, School of Medicine, Emory University, Atlanta, GA, USA; Department of Ophthalmology, School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Suma P
authors.initials: SP
authors.lastname: Shankar
authors.affiliation: Pediatric Gastroenterology Department, King Edward Memorial Hospital Research Centre, Pune, India.
authors.forename: Ashish
authors.initials: A
authors.lastname: Bavdekar
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.
authors.forename: Nicola
authors.initials: N
authors.lastname: Longo
authors.affiliation: Kaiser Permanente, Los Angeles, CA, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Mardach
authors.affiliation: Department of Gastroenterology, Hepatology, and Nutrition, UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Harmatz
authors.affiliation: Department of Biomedical, Industrial, & Human Factors Engineering, Wright State University, Dayton, OH, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hangartner
authors.affiliation: Biostatistics & Statistical Programming Department, Shire, Lexington, MA, USA.
authors.forename: Hak-Myung
authors.initials: HM
authors.lastname: Lee
authors.affiliation: Rare Disease Unit, Shire, Lexington, MA, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Crombez
authors.affiliation: Department of Medicine/National Centre for Inherited Metabolic Disorders, Mater Misericordiae University Hospital, Dublin, Ireland.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Pastores
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D056947:Enzyme Replacement Therapy; D005260:Female; D005776:Gaucher Disease / Q000188:drug therapy*; D005962:Glucosylceramidase / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D012741:Sexual Maturation; D016896:Treatment Outcome
chemical_list: D005962:Glucosylceramidase; C550184:Velaglucerase alfa, human; C090568:imiglucerase
keywords: Children and adolescents; Enzyme replacement therapy; Gaucher disease; Pediatric patients; Velaglucerase alfa