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

• Published in: Blood cells, molecules, & diseases molecules, & diseases, 2019-09, Vol.78, p.14-21
• Main Authors: Zimran, Ari, Durán, Gloria, Giraldo, Pilar, Rosenbaum, Hanna, Giona, Fiorina, Petakov, Milan, Terreros Muñoz, Eduardo, Solorio-Meza, Sergio Eduardo, Cooper, Peter A., Varughese, Sheeba, Alon, Sari, Chertkoff, Raul
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anemia; Biomarkers; Chemokine (C[sbnd]C motif) ligand 18; Chitotriosidase; Enzyme replacement therapy; Enzyme Replacement Therapy - methods; Female; Gaucher disease; Gaucher Disease - blood; Gaucher Disease - diagnosis; Gaucher Disease - drug therapy; Glucosylceramidase - administration & dosage; Glucosylceramidase - adverse effects; Glucosylceramidase - therapeutic use; Hepatomegaly; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Recombinant Proteins - administration & dosage; Recombinant Proteins - adverse effects; Recombinant Proteins - therapeutic use; Splenomegaly; Taliglucerase alfa; Thrombocytopenia; Treatment Outcome
• ISSN: 1079-9796; 1096-0961
• DOI: 10.1016/j.bcmd.2016.07.002

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.