title: Treatment-naïve Gaucher disease patients achieve therapeutic goals and normalization with velaglucerase alfa by 4years in phase 3 trials.
abstract: Gaucher disease is an inherited metabolic disease characterized by β-glucocerebrosidase deficiency and commonly treated with enzyme replacement therapy (ERT). The efficacy of ERT with velaglucerase alfa was assessed based on the achievement of published therapeutic goals and the normalization of disease parameters in 39 treatment-naïve patients with type 1 Gaucher disease, 6 to 62years of age, enrolled in phase 3 clinical trials. After 4years of ERT, therapeutic goals for thrombocytopenia and splenomegaly had been achieved in 100% of patients; goals for anemia and hepatomegaly had been achieved in 95% and 94% of patients, respectively. Consistent with the goal for bone mineral density, lumbar spine bone density improved in 87% of patients ≥18years of age. At year 4, compared with clinical ranges for healthy individuals, 86% of patients with a low baseline hemoglobin concentration had normalized, 60% with a low baseline platelet count had normalized, 67% with baseline splenomegaly had normalized, 58% with hepatomegaly had normalized, and lumbar spine bone density had normalized in 53% of adults. The decade-old therapeutic goals do not reflect the potential for normalization of clinical parameters in ERT-treated patients. Goals consistent with normalization or near-normalization should be considered. ClinicalTrials.gov identifiers: NCT00430625, NCT00553631, NCT00635427.
authors.affiliation: Gaucher Clinic, Shaare Zedek Medical Center, Hebrew University-Hadassah Medical School, Jerusalem, Israel. Electronic address: azimran@gmail.com.
authors.forename: Ari
authors.initials: A
authors.lastname: Zimran
authors.affiliation: Gaucher Clinic, Shaare Zedek Medical Center, Hebrew University-Hadassah Medical School, Jerusalem, Israel. Electronic address: delstein-c@shire.com.
authors.forename: Deborah
authors.initials: D
authors.lastname: Elstein
authors.affiliation: Instituto Privado de Hematología e Investigación Clínica (IPHIC), Asunción, Paraguay. Electronic address: gderlis@conexion.com.py.
authors.forename: Derlis E
authors.initials: DE
authors.lastname: Gonzalez
authors.affiliation: Department of Orphan Diseases, National Research Center for Hematology, Moscow, Russia. Electronic address: elenalukina02@gmail.com.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Lukina
authors.affiliation: Shire, Lexington, MA, USA. Electronic address: yqin@shire.com.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Shire, Lexington, MA, USA. Electronic address: qdinh@shire.com.
authors.forename: Quinn
authors.initials: Q
authors.lastname: Dinh
authors.affiliation: Paediatric Department, La Rabta Hospital, Tunis, Tunisia. Electronic address: hadhami.baili@laposte.net.
authors.forename: Hadhami Ben
authors.initials: HB
authors.lastname: Turkia
mesh_terms: D000293:Adolescent; D000328:Adult; D015519:Bone Density / Q000187:drug effects; D002648:Child; D004311:Double-Blind Method; D056947:Enzyme Replacement Therapy / Q000379:methods; D005260:Female; D005776:Gaucher Disease / Q000097:blood / Q000188:drug therapy*; D005962:Glucosylceramidase / Q000627:therapeutic use*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006454:Hemoglobins; D005962:Glucosylceramidase; C550184:Velaglucerase alfa, human
keywords: Gaucher disease; Normalization; Therapeutic goal; Velaglucerase alfa