Abstract
BackgroundGaucher disease (GD) is caused by reduced lysosomal enzyme β-glucocerebrosidase activity. Heterogeneous genotypes and phenotypes have been observed within GD types and across ethnicities. Enzyme replacement therapy is generally recommended for patients with type 1 GD, the least severe form of GD. In Japan, velaglucerase alfa has a broad indication covering type 1, 2 or 3 GD. MethodsAll patients with type 1, 2, or 3 GD administered velaglucerase alfa 60 U/kg every 2 weeks via intravenous infusion after its launch date in Japan in 2014, were enrolled in a non-interventional, observational post-marketing surveillance (PMS). Individual patient data were reported via case report forms (CRFs). Key safety endpoints investigated included the incidence of infusion-related reactions (IRRs), the safety of velaglucerase alfa in patients with types 2 and 3 GD, from patients under one year of age to elderly patients (≥ 65 years of age). Long-term efficacy was also assessed. ResultsIn total, 53 patients with GD were registered. CRFs were available for 41 (77.4%) patients at the 6-year interim analysis. Fourteen adverse drug reactions (ADRs) were reported in seven patients. All reported ADRs occurred in patients with type 2 GD. ADRs were reported by 63.6% (7/11) of patients with type 2 GD. Ten ADRs were reported in five patients aged < 4 years. No elderly patients experienced any ADR during the surveillance period. Five ADRs occurring in three (10.0%) patients were classified as IRRs, with one case of vomiting (moderate severity) resulting in treatment discontinuation. Ten serious adverse events were reported in five (16.7%) patients. Three fatal events were considered to be unrelated to treatment with velaglucerase alfa. Platelet counts increased after the administration of velaglucerase alfa and were generally maintained within the normal range over the administration period. Among eleven patients tested for neutralizing anti-velaglucerase alfa antibodies, two (18.2%) were assessed as positive results. ConclusionPMS data from patients with types 1–3 GD in Japan indicate that long-term treatment with velaglucerase alfa was well-tolerated and associated with increased platelet counts, which is consistent with observations made in studies outside of Japan.Trial registration: NCT03625882 registered July 2014.
Highlights
Gaucher disease (GD) is caused by reduced lysosomal enzyme β-glucocerebrosidase activity
All Adverse drug reaction (ADR) were reported in patients with type 2 GD; no ADRs were reported by patients with type 1 or type 3 GD
ADRs were reported by 63.6% of patients with type 2 GD and 10 ADRs were reported in five patients (83.3%) aged < 4 years, who experienced two ADRs each
Summary
Gaucher disease (GD) is caused by reduced lysosomal enzyme β-glucocerebrosidase activity. Enzyme replacement therapy is generally recommended for patients with type 1 GD, the least severe form of GD. Gaucher disease (GD) is a rare, autosomal recessive lipid storage disorder caused by mutations in the GBA1 gene, leading to reduced activity of the lysosomal enzyme β-glucocerebrosidase [1]. Type 1 is the most common and mildest form of GD, typically diagnosed during adolescence, whereas type 2 GD is characterized by both systemic involvement and severe neurological impairment presenting during infancy, which is often fatal by 1–3 years of age [1, 2, 4]. Type 3 GD is a highly heterogeneous form that generally presents during early childhood and is characterized by systemic manifestations and varying degrees of neurological involvement [1, 2, 4, 6]. Platelet count tests are routinely employed to monitor the efficacy of therapies for patients with GD [16,17,18]
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