Long-term safety and effectiveness of velaglucerase alfa in Gaucher disease: 6-year interim analysis of a post-marketing surveillance in Japan

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 s...

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Autores principales:	Rieko Sagara, Masahide Ishigaki, Manami Otsuka, Kei Murayama, Hiroyuki Ida, Jovelle Fernandez
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Enzyme replacement therapy Gaucher disease Glucosylceramidase Japan Surveillance Post-marketing Medicine R
Acceso en línea:	https://doaj.org/article/8d337695556a429a94e942a7534676ae
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spelling	oai:doaj.org-article:8d337695556a429a94e942a7534676ae2021-12-05T12:16:58ZLong-term safety and effectiveness of velaglucerase alfa in Gaucher disease: 6-year interim analysis of a post-marketing surveillance in Japan10.1186/s13023-021-02119-21750-1172https://doaj.org/article/8d337695556a429a94e942a7534676ae2021-12-01T00:00:00Zhttps://doi.org/10.1186/s13023-021-02119-2https://doaj.org/toc/1750-1172Abstract 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.Rieko SagaraMasahide IshigakiManami OtsukaKei MurayamaHiroyuki IdaJovelle FernandezBMCarticleEnzyme replacement therapyGaucher diseaseGlucosylceramidaseJapanSurveillancePost-marketingMedicineRENOrphanet Journal of Rare Diseases, Vol 16, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Enzyme replacement therapy Gaucher disease Glucosylceramidase Japan Surveillance Post-marketing Medicine R
spellingShingle	Enzyme replacement therapy Gaucher disease Glucosylceramidase Japan Surveillance Post-marketing Medicine R Rieko Sagara Masahide Ishigaki Manami Otsuka Kei Murayama Hiroyuki Ida Jovelle Fernandez Long-term safety and effectiveness of velaglucerase alfa in Gaucher disease: 6-year interim analysis of a post-marketing surveillance in Japan
description	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.
format	article
author	Rieko Sagara Masahide Ishigaki Manami Otsuka Kei Murayama Hiroyuki Ida Jovelle Fernandez
author_facet	Rieko Sagara Masahide Ishigaki Manami Otsuka Kei Murayama Hiroyuki Ida Jovelle Fernandez
author_sort	Rieko Sagara
title	Long-term safety and effectiveness of velaglucerase alfa in Gaucher disease: 6-year interim analysis of a post-marketing surveillance in Japan
title_short	Long-term safety and effectiveness of velaglucerase alfa in Gaucher disease: 6-year interim analysis of a post-marketing surveillance in Japan
title_full	Long-term safety and effectiveness of velaglucerase alfa in Gaucher disease: 6-year interim analysis of a post-marketing surveillance in Japan
title_fullStr	Long-term safety and effectiveness of velaglucerase alfa in Gaucher disease: 6-year interim analysis of a post-marketing surveillance in Japan
title_full_unstemmed	Long-term safety and effectiveness of velaglucerase alfa in Gaucher disease: 6-year interim analysis of a post-marketing surveillance in Japan
title_sort	long-term safety and effectiveness of velaglucerase alfa in gaucher disease: 6-year interim analysis of a post-marketing surveillance in japan
publisher	BMC
publishDate	2021
url	https://doaj.org/article/8d337695556a429a94e942a7534676ae
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Long-term safety and effectiveness of velaglucerase alfa in Gaucher disease: 6-year interim analysis of a post-marketing surveillance in Japan

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