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

Abstract

Gaucher disease (GD) is a lysosomal storage disorder; symptomatic patients with type 1 GD need long-term disease-specific therapy of which the standard of care has been enzyme replacement therapy (ERT). Thirtyeight of 40 patients (aged 9-71 years) clinically stable on ERT with imiglucerase, safely switched to a comparable dose of velaglucerase alfa (units/kg) during TKT034, a 12-month, open-label clinical study, and for 10-50 months in an extension study. The most common adverse events (AEs) judged to be drug-related in the extension were fatigue and bone pain. No drug-related serious AEs were reported. No AEs led to study withdrawal. At 24 months from baseline (baseline being TKT034 week 0), patients had generally stable hemoglobin, platelet, spleen, liver, and bone density parameters. Nevertheless, dose adjustment based on the achievement of therapeutic goals was permitted, and 10 patients, including seven patients who had platelet counts <100 3 10 9 /L at baseline, were given at least one 15 U/kg-dose increase during the extension. Trends indicative of improvement in platelet count and spleen volume, and decreasing levels of GD biomarkers, chitotriosidase and CCL18, were observed. Immunogenicity was seen in one patient positive for antiimiglucerase antibodies at baseline. This patient tested positive for anti-velaglucerase alfa antibodies in TKT034, with low antibody concentrations, and throughout the extension study; however, the patient continued to receive velaglucerase alfa without clinical deterioration. In conclusion, clinically stable patients can be switched from imiglucerase to velaglucerase alfa ERT and maintain or achieve good therapeutic outcomes.

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].…”

Rethinking fatigue in Gaucher disease

“…Elstein et al [24] reported long-term safety findings in 38 patients from an extension study of a phase II/III trial in which patients with GD switched treatment from imiglucerase to velaglucerase alfa. Fatigue was reported as an adverse event possibly or probably related to velaglucerase alfa treatment and as an infusion-associated reaction in 2 patients [24].…”

“…Elstein et al [24] reported long-term safety findings in 38 patients from an extension study of a phase II/III trial in which patients with GD switched treatment from imiglucerase to velaglucerase alfa. Fatigue was reported as an adverse event possibly or probably related to velaglucerase alfa treatment and as an infusion-associated reaction in 2 patients [24]. In an observational retrospective study of 99 French patients with GD, data regarding demographics, GD history, treatment, and biological and clinical characteristics were collected; other GD-related data could also be spontaneously reported by the investigators [25].…”

“…Fifteen manuscripts were published in English [11,[13][14][15][16][17][18][19][20][21][22][23][24][25][26], and the remaining 4 articles were published in German [27], French [28], Hungarian [29], and Danish [30]. For the articles published in German, French, Hungarian, or Danish, English-language abstracts were available and reviewed.…”