Long-term efficacy and safety results of taliglucerase alfa through 5years in adult treatment-naïve patients with Gaucher disease.

Abstract

Taliglucerase alfa, the first available plant cell-expressed recombinant therapeutic protein, is an enzyme replacement therapy approved for Gaucher disease (GD). PB-06-001, a pivotal phase 3, multicenter, randomized, double-blind, parallel-dose study investigated taliglucerase alfa 30 or 60U/kg every other week through 9months in treatment-naïve adults with GD; 30-month extension study PB-06-003 followed. Patients completing PB-06-001 and PB-06-003 could continue treatment in PB-06-007. Nineteen patients enrolled in PB-06-007 (30U/kg, n=8; 60U/kg, n=9; dose adjusted, n=2); 17 completed 5 total years of treatment. In these 3 groups, respectively, taliglucerase alfa resulted in mean decreases in spleen volume (-8.7, -6.9, -12.4 multiples of normal), liver volume (-0.6, -0.4, -0.5 multiples of normal), chitotriosidase activity (-83.1%, -93.4%, -87.9%), and chemokine (CC motif) ligand 18 concentration (-66.7%, -83.3%, -78.9%), as well as mean increases in hemoglobin concentration (+2.1, +2.1, +1.8mg/dL) and platelet count (+31,871, +106,800, +34,000/mm3). The most common adverse events were nasopharyngitis and arthralgia. Most adverse events were mild/moderate; no serious adverse events were considered treatment-related. These results demonstrate continued improvement of disease parameters during 5years of taliglucerase alfa therapy in 17 treatment-naive patients with no new safety concerns, extending the taliglucerase alfa clinical efficacy and safety dataset. This study was registered at www.clinicaltrials.gov as NCT01422187.

• Authors: Ari Zimran, Gloria Durán, Pilar Giraldo, Hanna Rosenbaum, Fiorina Giona, Milan Petakov, Eduardo Terreros Muñoz, Sergio Eduardo Solorio-Meza, Peter A Cooper, Sheeba Varughese, Sari Alon, Raul Chertkoff
• Journal: Blood cells, molecules & diseases (Blood Cells Mol Dis) Vol. 78 Pg. 14-21 (09 2019) ISSN: 1096-0961 [Electronic] United States
• PMID: 27499018 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Recombinant Proteins
• Glucosylceramidase
• taliglucerase alfa

Topics

• Adult
• Aged
• Biomarkers
• Enzyme Replacement Therapy (methods)
• Female
• Gaucher Disease (blood, diagnosis, drug therapy)
• Glucosylceramidase (administration & dosage, adverse effects, therapeutic use)
• Humans
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Recombinant Proteins (administration & dosage, adverse effects, therapeutic use)
• Treatment Outcome