Pivotal trial with plant cell-expressed recombinant glucocerebrosidase, taliglucerase alfa, a novel enzyme replacement therapy for Gaucher disease

Blood. 2011 Nov 24;118(22):5767-73. doi: 10.1182/blood-2011-07-366955. Epub 2011 Sep 6.

Abstract

Taliglucerase alfa (Protalix Biotherapeutics, Carmiel, Israel) is a novel plant cell-derived recombinant human β-glucocerebrosidase for Gaucher disease. A phase 3, double-blind, randomized, parallel-group, comparison-dose (30 vs 60 U/kg body weight/infusion) multinational clinical trial was undertaken. Institutional review board approvals were received. A 9-month, 20-infusion trial used inclusion/exclusion criteria in treatment-naive adult patients with splenomegaly and thrombocytopenia. Safety end points were drug-related adverse events: Ab formation and hypersensitivity reactions. Primary efficacy end point was reduction in splenic volume measured by magnetic resonance imaging. Secondary end points were: changes in hemoglobin, hepatic volume, and platelet counts. Exploratory parameters included biomarkers and bone imaging. Twenty-nine patients (11 centers) completed the protocol. There were no serious adverse events; drug-related adverse events were mild/moderate and transient. Two patients (6%) developed non-neutralizing IgG Abs; 2 other patients (6%) developed hypersensitivity reactions. Statistically significant spleen reduction was achieved at 9 months: 26.9% (95% confidence interval [CI]: -31.9, -21.8) in the 30-unit dose group and 38.0% (95% CI: -43.4, -32.8) in the 60-unit dose group (both P < .0001); and in all secondary efficacy end point measures, except platelet counts at the lower dose. These results support safety and efficacy of taliglucerase alfa for Gaucher disease.

Trial registration: ClinicalTrials.gov NCT00376168.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Algorithms
  • Double-Blind Method
  • Enzyme Replacement Therapy* / methods
  • Female
  • Gaucher Disease / drug therapy*
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Plant
  • Glucosylceramidase / genetics
  • Glucosylceramidase / metabolism
  • Glucosylceramidase / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Placebos
  • Plant Cells / enzymology
  • Plant Cells / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Transfection
  • Treatment Outcome
  • Young Adult

Substances

  • Placebos
  • Recombinant Proteins
  • Glucosylceramidase

Associated data

  • ClinicalTrials.gov/NCT00376168