title: Safety and efficacy results of switch from imiglucerase to velaglucerase alfa treatment in patients with type 1 Gaucher disease.
abstract: Gaucher disease (GD) is a lysosomal storage disorder; symptomatic patients with type 1 GD need long-term disease-specific therapy of which the standard of care has been enzyme replacement therapy (ERT). Thirty-eight of 40 patients (aged 9-71 years) clinically stable on ERT with imiglucerase, safely switched to a comparable dose of velaglucerase alfa (units/kg) during TKT034, a 12-month, open-label clinical study, and for 10-50 months in an extension study. The most common adverse events (AEs) judged to be drug-related in the extension were fatigue and bone pain. No drug-related serious AEs were reported. No AEs led to study withdrawal. At 24 months from baseline (baseline being TKT034 week 0), patients had generally stable hemoglobin, platelet, spleen, liver, and bone density parameters. Nevertheless, dose adjustment based on the achievement of therapeutic goals was permitted, and 10 patients, including seven patients who had platelet counts <100 × 10(9) /L at baseline, were given at least one 15 U/kg-dose increase during the extension. Trends indicative of improvement in platelet count and spleen volume, and decreasing levels of GD biomarkers, chitotriosidase and CCL18, were observed. Immunogenicity was seen in one patient positive for anti-imiglucerase antibodies at baseline. This patient tested positive for anti-velaglucerase alfa antibodies in TKT034, with low antibody concentrations, and throughout the extension study; however, the patient continued to receive velaglucerase alfa without clinical deterioration. In conclusion, clinically stable patients can be switched from imiglucerase to velaglucerase alfa ERT and maintain or achieve good therapeutic outcomes.
authors.affiliation: Gaucher Clinic, Shaare Zedek Medical Center, affiliated with the Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Deborah
authors.initials: D
authors.lastname: Elstein
authors.affiliation: Department of Haematology, Royal Free Hospital, London, United Kingdom.|Department of Haematology, University College London, London, United Kingdom.
authors.forename: Atul
authors.initials: A
authors.lastname: Mehta
authors.affiliation: Department of Haematology, Royal Free Hospital, London, United Kingdom.|Department of Haematology, University College London, London, United Kingdom.
authors.forename: Derralynn A
authors.initials: DA
authors.lastname: Hughes
authors.affiliation: Medicina Metabólica Hereditaria, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Zaragoza, Spain.|Grupo de Estudio de Enfermedades Hematologícas y Metabolicas, Hospital Universitario Miguel Servet, Zaragoza, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Giraldo
authors.affiliation: Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.
authors.forename: Joel
authors.initials: J
authors.lastname: Charrow
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, Missouri.
authors.forename: Laurie
authors.initials: L
authors.lastname: Smith
authors.affiliation: Departments of Human Genetics and Ophthalmology, School of Medicine, Emory University, Atlanta, Georgia.
authors.forename: Suma P
authors.initials: SP
authors.lastname: Shankar
authors.affiliation: Department of Biomedical, Industrial, & Human Factors Engineering, Wright State University, Dayton, Ohio.
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Hangartner
authors.affiliation: Bioanalytical and BioMarker Development, Shire, Lexington, Massachusetts.
authors.forename: Yune
authors.initials: Y
authors.lastname: Kunes
authors.affiliation: Biostatistics & Statistical Programming Department, Shire, Lexington, Massachusetts.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: Rare Disease Unit, Shire, Lexington, Massachusetts.
authors.forename: Eric
authors.initials: E
authors.lastname: Crombez
authors.affiliation: Gaucher Clinic, Shaare Zedek Medical Center, affiliated with the Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Ari
authors.initials: A
authors.lastname: Zimran
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015519:Bone Density / Q000187:drug effects; D019742:Chemokines, CC / Q000097:blood; D002648:Child; D004334:Drug Administration Schedule; D057915:Drug Substitution; D056947:Enzyme Replacement Therapy; D005260:Female; D005776:Gaucher Disease / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D005962:Glucosylceramidase / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism; D006596:Hexosaminidases / Q000097:blood; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009929:Organ Size / Q000187:drug effects; D010976:Platelet Count; D011446:Prospective Studies; D013154:Spleen / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C111792:CCL18 protein, human; D019742:Chemokines, CC; D006454:Hemoglobins; D007074:Immunoglobulin G; D006596:Hexosaminidases; C086400:chitotriosidase; D005962:Glucosylceramidase; C550184:Velaglucerase alfa, human; C090568:imiglucerase