title: Pivotal trial with plant cell-expressed recombinant glucocerebrosidase, taliglucerase alfa, a novel enzyme replacement therapy for Gaucher disease.
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.
authors: Gaucher Clinic, Shaare Zedek Medical Center, Hadassah Medical School, Hebrew University, Jerusalem, Israel. azimran@gmail.com
authors: Ari
authors: A
authors: Zimran
authors: Einat
authors: E
authors: Brill-Almon
authors: Raul
authors: R
authors: Chertkoff
authors: Milan
authors: M
authors: Petakov
authors: Francisco
authors: F
authors: Blanco-Favela
authors: Eduardo Terreros
authors: ET
authors: Muñoz
authors: Sergio E
authors: SE
authors: Solorio-Meza
authors: Dominick
authors: D
authors: Amato
authors: Gloria
authors: G
authors: Duran
authors: Fiorina
authors: F
authors: Giona
authors: Rene
authors: R
authors: Heitner
authors: Hanna
authors: H
authors: Rosenbaum
authors: Pilar
authors: P
authors: Giraldo
authors: Atul
authors: A
authors: Mehta
authors: Glen
authors: G
authors: Park
authors: Mici
authors: M
authors: Phillips
authors: Deborah
authors: D
authors: Elstein
authors: Gheona
authors: G
authors: Altarescu
authors: Mali
authors: M
authors: Szleifer
authors: Sharon
authors: S
authors: Hashmueli
authors: David
authors: D
authors: Aviezer
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D004311:Double-Blind Method; D056947:Enzyme Replacement Therapy / Q000379:methods; D005260:Female; D005776:Gaucher Disease / Q000188:drug therapy*; D015971:Gene Expression Regulation, Enzymologic; D018506:Gene Expression Regulation, Plant; D005962:Glucosylceramidase / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D059828:Plant Cells / Q000201:enzymology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D010919:Placebos; D011994:Recombinant Proteins; D005962:Glucosylceramidase