Velaglucerase alfa for Gaucher disease in Japan: Long-term post-marketing surveillance data from a unique population with high rates of neuronopathic subtypes

Gaucher disease (GD) is a rare, autosomal recessive disease with reduced β-glucocerebrosidase activity, leading to symptoms including hepatosplenomegaly, anemia, thrombocytopenia, and bone disease. Velaglucerase alfa is a native human β-glucocerebrosidase preparation approved as enzyme replacement therapy for Type 1 GD in many countries and for all GD types, including neuronopathic Type 2 and Type 3, in Japan. In this report, we provide the final (up to 8 years) safety and somatic effectiveness results of an all-case, open-label, post-marketing surveillance study in Japan. Among all patients, the incidence of adverse drug reactions (ADRs) was 23.3% (14/60 patients) and serious ADRs was 8.3% (5/60 patients). In the safety analysis population (excluding patients who did not provide consent for publication), ADR incidence was 19.5% (8/41 patients), most commonly vomiting and positive antibody test (4.9% [2/41 patients] each); one patient experienced vomiting as a serious ADR. ADRs were more common in Type 2 (7/14 patients) compared with Type 1 (1/12 patients) and Type 3 (0/15 patients). Three patients (7.3%), all Type 2, had five infusion-related reactions of pyrexia, vomiting (serious), swelling of eyelid, and hypersensitivity; all resolved or recovered. In the effectiveness analysis population (patients with any effectiveness data; n = 39), hemoglobin concentration, platelet count, and plasma angiotensin-converting enzyme concentration improved by Week 48 in patients with no prior GD treatment and were maintained in patients with prior GD treatment. These results support long-term use of velaglucerase alfa in Japanese patients with all GD types, with safety and somatic effectiveness consistent with previous findings.