title: Velaglucerase alfa (VPRIV) enzyme replacement therapy in patients with Gaucher disease: Long-term data from phase III clinical trials.
abstract: Type 1 Gaucher disease is an inherited lysosomal enzyme deficiency with variable age of symptom onset. Common presenting signs include thrombocytopenia, anemia, hepatosplenomegaly, bone abnormalities, and, additionally in children, growth failure. Fifty-seven patients aged 3-62 years at the baseline of two phase III trials for velaglucerase alfa treatment were enrolled in the single extension study. In the extension, they received every-other-week velaglucerase alfa intravenous infusions for 1.2-4.8 years at 60 U/kg, although 10 patients experienced dose reduction. No patient experienced a drug-related serious adverse event or withdrew due to an adverse event. One patient died following a convulsion that was reported as unrelated to the study drug. Only one patient tested positive for anti-velaglucerase alfa antibodies. Combining the experience of the initial phase III trials and the extension study, significant improvements were observed in the first 24 months from baseline in hematology variables, organ volumes, plasma biomarkers, and, in adults, the lumbar spine bone mineral density Z-score. Improvements were maintained over longer-term treatment. Velaglucerase alfa had a good long-term safety and tolerability profile, and patients continued to respond clinically, which is consistent with the results of the extension study to the phase I/II trial of velaglucerase alfa. EudraCT number 2008-001965-27; www.clinicaltrials.gov identifier NCT00635427.
authors: Department of Haematology, Royal Free Hospital, London, United Kingdom.|Department of Haematology, University College London, London, United Kingdom.
authors: Derralynn A
authors: DA
authors: Hughes
authors: Instituto Privado de Hematología e Investigación Clínica - IPHIC, Asunción, Paraguay.
authors: Derlis E
authors: DE
authors: Gonzalez
authors: Department of Orphan Diseases, Hematology Research Center, Moscow, Russia.
authors: Elena A
authors: EA
authors: Lukina
authors: Department of Haematology, Royal Free Hospital, London, United Kingdom.|Department of Haematology, University College London, London, United Kingdom.
authors: Atul
authors: A
authors: Mehta
authors: Pediatrics Department, All India Institute of Medical Sciences, New Delhi, India.
authors: Madhulika
authors: M
authors: Kabra
authors: Gaucher Clinic, Shaare Zedek Medical Center, affiliated with the Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors: Deborah
authors: D
authors: Elstein
authors: Hematology Department, Your Health SA, Buenos Aires, Argentina.
authors: Isaac
authors: I
authors: Kisinovsky
authors: Medicina Metabólica Hereditaria, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Zaragoza, Spain.|Grupo de Estudio de Enfermedades Hematologícas y Metabolicas, Hospital Universitario Miguel Servet, Zaragoza, Spain.
authors: Pilar
authors: P
authors: Giraldo
authors: Pediatric Gastroenterology Department, King Edward Memorial Hospital Research Centre, Pune, India.
authors: Ashish
authors: A
authors: Bavdekar
authors: Department of Biomedical, Industrial, & Human Factors Engineering, Wright State University, Dayton, Ohio.
authors: Thomas N
authors: TN
authors: Hangartner
authors: Biostatistics & Statistical Programming Department, Shire, Lexington, Massachusetts.
authors: Nan
authors: N
authors: Wang
authors: Rare Disease Unit, Shire, Lexington, Massachusetts.
authors: Eric
authors: E
authors: Crombez
authors: Gaucher Clinic, Shaare Zedek Medical Center, affiliated with the Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors: Ari
authors: A
authors: Zimran
mesh_terms: D000293:Adolescent; D000328:Adult; D015519:Bone Density / Q000187:drug effects; D019742:Chemokines, CC / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D056947:Enzyme Replacement Therapy; D005260:Female; D005776:Gaucher Disease / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D005962:Glucosylceramidase / Q000008:administration & dosage* / Q000009:adverse effects; D006596:Hexosaminidases / Q000097:blood; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009929:Organ Size / Q000187:drug effects; D011446:Prospective Studies; D013154:Spleen / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D016896:Treatment Outcome
chemical_list: C111792:CCL18 protein, human; D019742:Chemokines, CC; D007074:Immunoglobulin G; D006596:Hexosaminidases; C086400:chitotriosidase; D005962:Glucosylceramidase; C550184:Velaglucerase alfa, human