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: Deborah Elstein, Atul Mehta, Derralynn A Hughes, Pilar Giraldo, Joel Charrow, Laurie Smith, Suma P Shankar, Thomas N Hangartner, Yune Kunes, Nan Wang, Eric Crombez, Ari Zimran
• Journal: American journal of hematology (Am J Hematol) Vol. 90 Issue 7 Pg. 592-7 (Jul 2015) ISSN: 1096-8652 [Electronic] United States
• PMID: 25776130 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc.

Chemical References

• CCL18 protein, human
• Chemokines, CC
• Hemoglobins
• Immunoglobulin G
• Hexosaminidases
• chitotriosidase
• Glucosylceramidase
• Velaglucerase alfa, human
• imiglucerase

Topics

• Adolescent
• Adult
• Aged
• Bone Density (drug effects)
• Chemokines, CC (blood)
• Child
• Drug Administration Schedule
• Drug Substitution
• Enzyme Replacement Therapy
• Female
• Gaucher Disease (drug therapy, enzymology, pathology)
• Glucosylceramidase (therapeutic use)
• Hemoglobins (metabolism)
• Hexosaminidases (blood)
• Humans
• Immunoglobulin G (blood)
• Liver (drug effects, enzymology, pathology)
• Male
• Middle Aged
• Organ Size (drug effects)
• Platelet Count
• Prospective Studies
• Spleen (drug effects, enzymology, pathology)
• Treatment Outcome
• Young Adult