title: 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: Gaucher Clinic, Shaare Zedek Medical Center, Hebrew University and Hadassah Medical School, Jerusalem, Israel. Electronic address: azimran@gmail.com.
authors: Ari
authors: A
authors: Zimran
authors: Pontificia Universidad Catolica de Chile, Santiago, Chile.
authors: Gloria
authors: G
authors: Durán
authors: CIBERER, Hospital Universitario Miguel Servet, IIS Aragón, Zaragoza, Spain.
authors: Pilar
authors: P
authors: Giraldo
authors: Rambam Medical Center, Haifa, Israel.
authors: Hanna
authors: H
authors: Rosenbaum
authors: Sapienza University, Rome, Italy.
authors: Fiorina
authors: F
authors: Giona
authors: Clinical Center of Serbia, Clinic of Endocrinology, Diabetes and Metabolic Disease, Belgrade University Medical School, Belgrade, Serbia.
authors: Milan
authors: M
authors: Petakov
authors: Centro Médico Nacional Siglo XXI, Servicio de Hematologia, Mexico City, Mexico.
authors: Eduardo
authors: E
authors: Terreros Muñoz
authors: Hospital de Especialidades No1, Leon, Mexico.
authors: Sergio Eduardo
authors: SE
authors: Solorio-Meza
authors: Faculty of Health Sciences, University of the Witwatersrand, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa.
authors: Peter A
authors: PA
authors: Cooper
authors: Faculty of Health Sciences, University of the Witwatersrand, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa.
authors: Sheeba
authors: S
authors: Varughese
authors: Protalix BioTherapeutics, Carmiel, Israel.
authors: Sari
authors: S
authors: Alon
authors: Protalix BioTherapeutics, Carmiel, Israel.
authors: Raul
authors: R
authors: Chertkoff
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D056947:Enzyme Replacement Therapy / Q000379:methods; D005260:Female; D005776:Gaucher Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D005962:Glucosylceramidase / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D011994:Recombinant Proteins; D005962:Glucosylceramidase; C582473:taliglucerase alfa
keywords: Anemia; Chemokine (CC motif) ligand 18; Chitotriosidase; Enzyme replacement therapy; Gaucher disease; Hepatomegaly; Splenomegaly; Taliglucerase alfa; Thrombocytopenia