title: A multicenter open-label treatment protocol (HGT-GCB-058) of velaglucerase alfa enzyme replacement therapy in patients with Gaucher disease type 1: safety and tolerability.
abstract: OBJECTIVE
  To evaluate the safety of velaglucerase alfa in patients with type 1 Gaucher disease who received velaglucerase alfa in the US treatment protocol HGT-GCB-058 (ClinicalTrials.gov identifier NCT00954460) during a global supply shortage of imiglucerase.
  
  
  METHODS
  This multicenter open-label treatment protocol enrolled patients who were either treatment naïve or had been receiving imiglucerase. Patients received intravenous velaglucerase alfa every other week at a dose of 60 U/kg (treatment naïve) or 15-60 U/kg (previously treated).
  
  
  RESULTS
  A total of 211 (including six treatment-naïve) patients were enrolled. Among the 205 previously treated patients, 35 (17.1%) experienced an adverse event considered related to study drug. Among the six treatment-naïve patients, one had an adverse event considered related to study drug. Infusion-related adverse events occurred in 28 (13.3%) of the 211 patients and usually occurred during the first three infusions. De novo, nonneutralizing, anti-velaglucerase alfa antibodies developed during treatment in one (<1.0%) previously treated patient and none of the treatment-naïve patients.
  
  
  CONCLUSIONS
  The currently observed safety profile was consistent with those previously reported for imiglucerase and velaglucerase alfa phase III clinical trials. These results support the safety of initiating treatment with velaglucerase alfa or transitioning patients from imiglucerase therapy to velaglucerase alfa therapy.
authors.affiliation: Departments of Neurology and Pediatrics, New York University School of Medicine, New York, New York, USA.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Pastores
authors.affiliation: Cedars-Sinai/Tower Hematology Oncology, Beverly Hills, California, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Rosenbloom
authors.affiliation: University Research Foundation for Lysosomal Storage Diseases, Coral Springs, Florida, USA.
authors.forename: Neal
authors.initials: N
authors.lastname: Weinreb
authors.affiliation: Lysosomal Research and Treatment Unit, Fairfax, Virginia, USA.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Goker-Alpan
authors.affiliation: Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Grabowski
authors.affiliation: Shire, Lexington, Massachusetts, USA.
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Cohn
authors.affiliation: Shire, Lexington, Massachusetts, USA.
authors.forename: David
authors.initials: D
authors.lastname: Zahrieh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood / Q000276:immunology; D002648:Child; D056947:Enzyme Replacement Therapy; D005260:Female; D005776:Gaucher Disease / Q000188:drug therapy*; D005962:Glucosylceramidase / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000906:Antibodies; D011994:Recombinant Proteins; D005962:Glucosylceramidase; C550184:Velaglucerase alfa, human; C090568:imiglucerase