Long-term safety and efficacy of agalsidase beta in Japanese patients with Fabry disease: aggregate data from two post-authorization safety studies

Abstract

Background: Enzyme replacement therapy in Fabry disease has been available in Japan since 2004. Two post-authorization safety studies were conducted to evaluate agalsidase beta in Japanese patients with Fabry disease in real-world practice.Research Design and Methods: The Special Drug Use Investigation monitored the long-term safety and efficacy of agalsidase beta, and the Drug Use Investigation monitored safety in patients not participating in the Special Drug Use Investigation. Safety and efficacy evaluations included adverse drug reactions (ADRs), infusion-associated reactions and hypersensitivity reactions, and change in blood GL-3 level over time. Results: Of 396 patients in the aggregated data set, safety and efficacy analysis sets comprised 307 and 196 patients, respectively. ADRs occurred in 93 (30.3%) patients and serious ADRs occurred in 25 (8.1%) patients, with general disorders and administration site conditions (n=55, 17.9%), nervous system disorders (n=30, 9.8%) and skin and subcutaneous tissue disorders (n=23, 7.5%) the most common.Reductions in blood GL-3 levels occurred over the study, irrespective of age or disease phenotype. Conclusions: Agalsidase beta demonstrated acceptable safety and tolerability, with sustained reductions in blood GL-3 levelsin Japanese patients with Fabry disease in real-world clinical practice Clinical Trial Registration: NCT00233870/AGAL03004 (Special Drug Use Investigation of Agalsidase beta) ARTICLE HISTORY

Hypersensitivity reaction during enzyme replacement therapy in lysosomal storage disorders. A systematic review of desensitization strategies

“…Data on ERT are available for Fabry disease (agalsidase α and agalsidase β) and Gaucher disease (imiglucerase). HR occurred in about 16%–30% of patients who started these treatments 14–16 and desensitization for these enzymes has been attempted in eight patients, four with Fabry disease and four with Gaucher disease, respectively (Table 5). Four out of eight patients (50%) had positive skin test. Five patients tolerated the desensitization procedure (62.5%) Three out of eight patients (37.5%) had a breakthrough reaction during the first desensitization procedure.…”

“…Data on ERT are available for Fabry disease (agalsidase α and agalsidase β) and Gaucher disease (imiglucerase). HR occurred in about 16%-30% of patients who started these treatments [14][15][16] and desensitization for these enzymes has been attempted in eight patients, four with Fabry disease and four with Gaucher disease, respectively (Table 5).…”

Safety and tolerability of agalsidase beta infusions shorter than 90 minutes in patients with Fabry disease: post-hoc analysis of a Japanese post-marketing study

“…Post-hoc analyses of the long-term use safety data from the Special Drug Use Investigation of agalsidase beta study (Registry number: AGAL03004) and all-case surveillance data of patients enrolled in the Drug Use Investigation of agalsidase beta (Registry number: AGAL02904) were conducted to evaluate the safety and tolerability of infusion rate escalation among patients receiving agalsidase beta; details of these post-authorization safety studies have been described previously. (24) Selection criteria for patients enrolled in the Special Drug Use Investigation of agalsidase beta or the Drug Use Investigation of agalsidase beta have been previously published. ( 24) Brie y, Japanese patients with Fabry disease diagnosed by a physician according to de cient α-GalA activity or the identi cation of GLA gene mutation were eligible for inclusion.…”

Safety and tolerability of agalsidase beta infusions shorter than 90 min in patients with Fabry disease: post-hoc analysis of a Japanese post-marketing study

“…Post-hoc analyses of the long-term use safety data from the Special Drug Use Investigation of agalsidase beta study (Registry number: AGAL03004) and all-case surveillance data of patients enrolled in the Drug Use Investigation of agalsidase beta (Registry number: AGAL02904) were conducted to evaluate the safety and tolerability of infusion rate escalation among patients receiving agalsidase beta infusions in a hospital setting; details of these post-authorization safety studies have been described previously [ 24 ].…”

“…Selection criteria for patients enrolled in the Special Drug Use Investigation of agalsidase beta or the Drug Use Investigation of agalsidase beta have been previously published [ 24 ]. Briefly, Japanese patients with Fabry disease diagnosed by a physician according to deficient α-GalA activity or the identification of GLA gene mutation were eligible for inclusion.…”