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 × 109/L (P=0.002); 45 U/kg: +66.4%; +40.9 × 109/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. Am. J. Hematol. 88:166–171, 2013. © 2012 Wiley Periodicals, Inc.

Safety and efficacy results of switch from imiglucerase to velaglucerase alfa treatment in patients with type 1 Gaucher disease

“…HGT-GCB-044 was an open-label extension of three clinical trials of velaglucerase alfa in patients with type 1 GD. Two of the three trials enrolled treatment-na€ ıve patients, the results of which are reported elsewhere [7,8]. We report the extension study results of the cohort who completed the trial TKT034 [6], which was conducted in patients previously treated with imiglucerase.…”

Seven‐year safety and efficacy with velaglucerase alfa for treatment‐naïve adult patients with type 1 Gaucher disease

“…Collectively, these studies demonstrated that velaglucerase alfa was generally well tolerated among both treatment‐naïve and switch patients including children, adults, pregnant patients, and geriatric patients 2, 3, 4, 5, 6. There were few drug‐related serious adverse events (AEs) and the vast majority of AEs were classified by the investigators as infusion related and considered to be mild to moderate and transient in nature.…”

“…One case of anaphylactoid reaction was reported (<1%) 5. Overall, <1% of patients developed anti‐drug antibodies following exposure to velaglucerase alfa and no patients developed IgE antibodies 2, 3, 4, 5, 6.…”

“…TKT032 was a 12‐month, two‐arm, multicenter trial designed to evaluate two doses of intravenous velaglucerase alfa (45 U/kg or 60 U/kg, EOW), whereas HGT‐GCB‐039 was a 9‐month, two‐arm noninferiority trial with imiglucerase (Cerezyme®, Genzyme Corp, Cambridge, MA) serving as an active comparator 3, 4. In addition, a phase II/III trial, TKT034, was conducted as a 12‐month, single‐arm, open‐label multicenter trial examining the safety and efficacy of velaglucerase alfa in a population of clinically stable pediatric and adult patients with GD1 switched from imiglucerase to velaglucerase alfa at their previously stable dose 5.…”

Variation in chitotriosidase values measured on simultaneous samples by two commercial laboratories

“…There have been several recent publications describing the effects of velaglucerase alfa and comparing these with imiglucerase [1][2][3], thus expanding the options available to clinicians who considering enzyme replacement therapy for their patients. With recent drug shortages, there have been patients who have switched from products made by one manufacturer to the other and, at the time of the switch, the laboratory providing the chitotriosidase measurement may change.…”