No abstract

Background Gaucher 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.  Methods All 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.  Results In 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.  Conclusion PMS 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.

Background Gaucher disease (GD) is an autosomal recessive disease caused by GBA1 mutations resulting in glucosylceramide accumulation in macrophages. GD is characterized by hepatosplenomegaly, anemia, thrombocytopenia, bone complications, and neurological complications. Glucosylsphingosine (lyso-Gb1), a deacylated form of glucosylceramide, has been identified as a promising biomarker for the diagnosis and treatment response in GD. The aim of this study was to examine the relationship between plasma lyso-Gb1 and therapeutic goals for GD (improvements in hepatomegaly, splenomegaly, anemia, thrombocytopenia, bone pain, and bone crisis), as well as disease type and GBA1 mutation type, in Japanese patients with GD receiving velaglucerase alfa, an enzyme replacement therapy (ERT). Furthermore, this study compared the plasma lyso-Gb1 concentration observed in Japanese patients included in this study with that observed in a previous non-Japanese clinical study. Results This non-interventional, open-label, multicenter observational cohort study (October 2020 to March 2021) included a total of 20 patients (of any age) with GD (type 1: n = 8; type 2: n = 9; type 3: n = 3) treated with velaglucerase alfa for ≥ 3 months. Median (minimum–maximum) duration of velaglucerase alfa treatment was 49.5 (3–107) months. A total of 14 (70.0%) patients achieved all therapeutic goals (i.e., 100% achievement; improvements in hepatomegaly, splenomegaly, anemia, thrombocytopenia, bone pain, and bone crisis). Overall, median (minimum–maximum) lyso-Gb1 concentration was 24.3 (2.1–150) ng/mL. Although not statistically significant, numerically lower plasma lyso-Gb1 concentrations were observed in patients with 100% achievement compared with those without; no statistically significant difference in plasma lyso-Gb1 concentration was observed between patients with different disease type or mutation type. Furthermore, lyso-Gb1 concentrations observed in Japanese patients were numerically lower than that observed in a previous study of non-Japanese patients with GD receiving ERT. Conclusions In this study, high achievement rates of therapeutic goals with low lyso-Gb1 concentration were observed, demonstrating a correlation between therapeutic goals and lower plasma lyso-Gb1 concentration in Japanese patients with GD treated with velaglucerase alfa. This study further suggests that plasma lyso-Gb1 concentration may be a useful biomarker for treatment response in patients with GD.

No abstract

Background Gaucher disease (GD) is a rare, inherited metabolic disorder resulting from glucocerebrosidase deficiency. Patients benefit from early treatment as complications can arise from delayed diagnosis. Aims To measure GD awareness among Japanese haematologists and gastroenterologists, who are the specialists most likely to encounter patients with symptoms recognised in the Gaucher Earlier Diagnosis Consensus (GED‐C), such as hepatosplenomegaly and thrombocytopenia. Additionally, we aimed to determine key signs from the GED‐C associated with early diagnosis. Methods A quantitative web survey assessed Japanese haematologists and gastroenterologists for their (i) basic awareness of GD, (ii) explicit awareness of GD signs, (iii) explicit awareness of GD treatments and (iv) accuracy in suspecting GD in model patients. Results Survey results from 160 haematologists and 166 gastroenterologists indicated that more than 50% of haematologists were aware of GD symptoms, diagnostic criteria and/or treatments, and 38% of them had experienced or suspected GD. The majority of gastroenterologists were unaware of GD or knew the disease only by name, with 20% experiencing or suspecting GD in practice. Almost 70% of haematologists knew of enzyme replacement therapy, while 47% of gastroenterologists were not aware of any treatments for GD. Of the GED‐C items, an awareness of bone‐associated signs was correlated with accurate GD diagnosis in model patients and this awareness was greater among haematologists than gastroenterologists. Conclusions The present study showed that haematologists had greater awareness of GD than gastroenterologists, and that bone pain may be a key sign of GD to enhance early diagnosis.