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; http://www.clinicaltrials.gov identifier NCT00635427. Am. J. Hematol. 90:584–591, 2015. © 2015 Wiley Periodicals, Inc.

Long-term velaglucerase alfa treatment in children with Gaucher disease type 1 naïve to enzyme replacement therapy or previously treated with imiglucerase

“…The safety results from this subgroup analysis are consistent with those in the complete extension study population of 95 adult and pediatric patients [15,16]. No new safety concerns were identified in the pediatric subgroup.…”

“…In the Switch population, primary efficacy parameters were stable over time. The efficacy results in the pediatric population reflect those seen in the complete extension study population, where Overall Vela and Imi-Vela patients showed significant improvements in hematological parameters and organ volumes during the first 24 months that were maintained with longer-term treatment [16]; these efficacy parameters were generally stable in the complete Switch population [15].…”

Diagnosis and Management of Gaucher Disease in India – Consensus Guidelines of the Gaucher Disease Task Force of the Society for Indian Academy of Medical Genetics and the Indian Academy of Pediatrics

“…Enzyme Replacement Therapy: The development and availability of ERT since 1991 as a treatment modality has transformed the natural course of the disease in patients affected with GD. Therapy with ERT significantly ameliorates organomegaly and improves hematological manifestations [34][35][36], as also the skeletal manifestations, prevent avascular necrosis, and reverse, growth failure in Gaucher disease type 1 [37][38][39]. A longitudinal cohort study of 25 children with GD1 and GD3 with 14 years follow-up reinforced previous reports and showed sustained improvement in hemoglobin, platelet count and bone pain [40].…”

Doença De Gaucher Tipo 1 No Esqueleto: Revisão Da América Latina

“…61 In our review of studies including Latin American patients undergoing intervention for Gaucher disease, we summarized the studies that had two time points at which patients underwent an intervention, and examined the outcome on skeletal manifestations. These studies 29,30,33,[62][63][64][65][66] showed similar outcomes to the international literature and consensus 59 providing evidence that treatment, especially early intervention, improves skeletal outcomes. (Table 2) …”