title: A Phase 3, multicenter, open-label, switchover trial to assess the safety and efficacy of taliglucerase alfa, a plant cell-expressed recombinant human glucocerebrosidase, in adult and pediatric patients with Gaucher disease previously treated with imiglucerase.
abstract: Taliglucerase alfa is a β-glucosidase enzyme replacement therapy (ERT) approved in the US and other countries for the treatment of Gaucher disease (GD) in adults and is approved in pediatric and adult patients in Australia and Canada. It is the first approved plant cell-expressed recombinant human protein. A Phase 3, multicenter, open-label, 9-month study assessed safety and efficacy of switching to taliglucerase alfa in adult and pediatric patients with GD treated with imiglucerase for at least the previous 2years. Patients with stable disease were offered taliglucerase alfa treatment using the same dose (9-60U/kg body weight) and regimen of administration (every 2weeks) as imiglucerase. This report summarizes results from 26 adult and 5 pediatric patients who participated in the trial. Disease parameters (spleen and liver volumes, hemoglobin concentration, platelet count, and biomarker levels) remained stable through 9months of treatment in adults and children following the switch from imiglucerase. All treatment-related adverse events were mild or moderate in severity and transient in nature. Exploratory parameters of linear growth and development showed positive outcomes in pediatric patients. These findings provide evidence of the efficacy and safety profile of taliglucerase alfa as an ERT for GD in patients previously treated with imiglucerase. This trial was registered at www.clinicaltrials.gov as # NCT00712348.
authors.affiliation: New York University School of Medicine, Neurogenetics Unit, 403 E 34th St, Suite 2, New York, NY 10016 USA. Electronic address: gpastores@mater.ie.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Pastores
authors.affiliation: Belgrade University Medical School, Dr Subotica 13, Belgrade 11000, Serbia; Clinic for Endocrinology, Clinical Center of Serbia, Institute of Endocrinology, Diabetes and Metabolic Diseases, Belgrade, Serbia. Electronic address: mpetakov@EUnet.rs.
authors.forename: Milan
authors.initials: M
authors.lastname: Petakov
authors.affiliation: Hospital Universitario Miguel Servet, CIBERER, Paseo de Isabel La Católica 1-3, Zaragoza 50009, Spain. Electronic address: giraldocastellano@gmail.com.
authors.forename: Pilar
authors.initials: P
authors.lastname: Giraldo
authors.affiliation: Hematology Department, Rambam Health Care Campus, 8 Haaliya Street, Haifa 31096, Israel. Electronic address: roseerlich@gmail.com.
authors.forename: Hanna
authors.initials: H
authors.lastname: Rosenbaum
authors.affiliation: Royal Melbourne Hospital, 300 Grattan Street, Parkville, Victoria 3050, Australia. Electronic address: jeff.szer@mh.org.au.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Szer
authors.affiliation: Lysosomal Diseases Unit, Addenbrooke's Hospital, Department of Medicine, University of Cambridge, Level 5, (Box 157) Hills Road, Cambridge, Cambridgeshire CB2 2QQ, UK. Electronic address: patrick.deegan@addenbrookes.nhs.uk.
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Deegan
authors.affiliation: Mount Sinai Hospital, Joseph and Wolf Lebovic Health Complex, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada. Electronic address: damato@mtsinai.on.ca.
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Amato
authors.affiliation: Gutenberg-University Mainz, Saarstrasse 21, Mainz D 55099, Germany. Electronic address: mengel@kinder.klinik.uni-mainz.de.
authors.forename: Eugen
authors.initials: E
authors.lastname: Mengel
authors.affiliation: KK Women's and Children's Hospital, Department of Paediatric Medicine, 100 Bukit Timah Road, 229899, Singapore. Electronic address: tan.ee.shien@kkh.com.sg.
authors.forename: Ee Shien
authors.initials: ES
authors.lastname: Tan
authors.affiliation: Protalix BioTherapeutics, 2 Snunit St., Science Park, POB 455 Carmiel, Israel. Electronic address: raul@protalix.com.
authors.forename: Raul
authors.initials: R
authors.lastname: Chertkoff
authors.affiliation: Protalix BioTherapeutics, 2 Snunit St., Science Park, POB 455 Carmiel, Israel. Electronic address: einata@protalix.com.
authors.forename: Einat
authors.initials: E
authors.lastname: Brill-Almon
authors.affiliation: Gaucher Clinic, Shaare Zedek Medical Center, 12 Bayit Street, Jerusalem 91031, Israel. Electronic address: Azimran@gmail.com.
authors.forename: Ari
authors.initials: A
authors.lastname: Zimran
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects; D002648:Child; D057915:Drug Substitution; D056947:Enzyme Replacement Therapy; D005776:Gaucher Disease / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D015870:Gene Expression; D005962:Glucosylceramidase / Q000096:biosynthesis / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D010976:Platelet Count; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000627:therapeutic use; D013154:Spleen / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D055815:Young Adult; D001617:beta-Glucosidase / Q000172:deficiency* / Q000235:genetics
chemical_list: D006454:Hemoglobins; D011994:Recombinant Proteins; D001617:beta-Glucosidase; D005962:Glucosylceramidase; C582473:taliglucerase alfa; C090568:imiglucerase
keywords: Enzyme replacement therapy; Gaucher disease; Imiglucerase; Taliglucerase alfa