title: Enzyme replacement therapy with velaglucerase alfa in Gaucher disease: Results from a randomized, double-blind, multinational, Phase 3 study.
abstract: Type 1 Gaucher disease (GD1), resulting from glucocerebrosidase deficiency, leads to splenomegaly, hepatomegaly, anemia, thrombocytopenia, and bone involvement. Current standard treatment is enzyme replacement therapy. Velaglucerase alfa is an enzyme replacement product for GD1, with the same amino acid sequence as naturally occurring human glucocerebrosidase. This multinational, Phase 3 trial evaluated the efficacy and safety of two doses of velaglucerase alfa in 25 treatment-naïve, anemic patients with GD1 (4-62 years of age), randomized to intravenous velaglucerase alfa 60 U/kg (n=12) or 45 U/kg body weight (n=13) every other week for 12 months. The primary endpoint was change from baseline in hemoglobin concentration in the 60 U/kg arm. At 12 months, mean hemoglobin concentrations increased from baseline [60 U/kg: +23.3%; +2.43 g/dL (P<0.001); 45 U/kg: +23.8%; +2.44 g/dL (P<0.001)], as did mean platelet counts [60 U/kg: +65.9%; +50.9 × 10(9) /L (P=0.002); 45 U/kg: +66.4%; +40.9 × 10(9) /L(P=0.01)]. Mean splenic volume decreased from baseline [60 U/kg: -50.4%, from 14.0 to 5.8 multiples of normal (MN) (P=0.003); 45 U/kg: -39.9%, from 14.5 to 9.5 MN (P=0.009)]. No drug-related serious adverse events or withdrawals were observed. One patient developed antibodies. Velaglucerase alfa was generally well tolerated and effective for adults and children with GD1 in this study. All disease-specific parameters measured demonstrated clinically meaningful improvements after 12 months.
authors: Sanatorio Español, Asunción, Paraguay.
authors: Derlis E
authors: DE
authors: Gonzalez
authors: Hadhami Ben
authors: HB
authors: Turkia
authors: Elena A
authors: EA
authors: Lukina
authors: Isaac
authors: I
authors: Kisinovsky
authors: Marie-Françoise Ben
authors: MF
authors: Dridi
authors: Deborah
authors: D
authors: Elstein
authors: David
authors: D
authors: Zahrieh
authors: Eric
authors: E
authors: Crombez
authors: Kiran
authors: K
authors: Bhirangi
authors: Norman W
authors: NW
authors: Barton
authors: Ari
authors: A
authors: Zimran
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D056947:Enzyme Replacement Therapy; D005260:Female; D005776:Gaucher Disease / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D005962:Glucosylceramidase / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D006454:Hemoglobins; D011994:Recombinant Proteins; D005962:Glucosylceramidase; C550184:Velaglucerase alfa, human