Velaglucerase alfa enzyme replacement therapy compared with imiglucerase in patients with Gaucher disease
Open accessAbstract
Enzyme replacement therapy for Gaucher disease (GD) has been available since 1991. This study compared the efficacy and safety of velaglucerase alfa with imiglucerase, the previous standard of care. A 9‐month, global, randomized, double‐blind, non‐inferiority study compared velaglucerase alfa with imiglucerase (60 U/kg every other week) in treatment‐naïve patients aged 3–73 years with anemia and either thrombocytopenia or organomegaly. The primary endpoint was the difference between groups in mean change from baseline to 9 months in hemoglobin concentration. 35 patients were randomized: 34 received study drug (intent‐to‐treat: 17 per arm), 20 were splenectomized. Baseline characteristics were similar in the two groups. The per‐protocol population included 15 patients per arm. The mean treatment difference for hemoglobin concentration from baseline to 9 months (velaglucerase alfa minus imiglucerase) was 0.14 and 0.16 g/dL in the intent‐to‐treat and per‐protocol populations, respectively. The lower bound of the 97.5% one‐sided confidence interval in both populations lay within the pre‐defined non‐inferiority margin of −1.0 g/dL, confirming that velaglucerase alfa is non‐inferior to imiglucerase. There were no statistically significant differences in the secondary endpoints. Most adverse events were mild to moderate. No patient receiving velaglucerase alfa developed antibodies to either drug, whereas four patients (23.5%) receiving imiglucerase developed IgG antibodies to imiglucerase, which were cross‐reactive with velaglucerase alfa in one patient. This study demonstrates the efficacy and safety of velaglucerase alfa compared with imiglucerase in adult and pediatric patients with GD clinically characterized as Type 1. Differences in immunogenicity were also observed. Am. J. Hematol. 88:179–184, 2013. © 2012 Wiley Periodicals, Inc.
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Velaglucerase alfa and other β-glucocerebrosidases produced in CHO and carrot cells show diverse glycan profiles but similar macrophage uptake, in vitro enzymatic activity, stability, and efficacy.
“Even though these three products show diverse glycan profiles, they showed similar macrophage uptake, in vitro enzymatic activity, stability and efficacy (Ben Turkia et al., 2013;Tekoah et al., 2013).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Ben Turkia et al., 2013
The Introduction (page not specified) describes different glycan compositions, while the trial results report non-inferior clinical efficacy for velaglucerase alfa versus imiglucerase. But the Introduction says velaglucerase alfa enters cultured human macrophages more rapidly, not at a similar rate. This paper does not establish comparable in vitro activity or stability, or compare a carrot-cell product. (LLM, conf=0.90)
Experimental — accuracy not yet measuredNeutralizing anti-Imiglucerase antibodies were observed in 24% of patients, with an impact on the protein activity.
“Notably, neutralizing anti-Imiglucerase antibodies were observed in 24% of patients, with an impact on the protein activity (Ben Turkia et al., 2013).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Ben Turkia et al., 2013
The Discussion reports anti-imiglucerase antibodies in 23.5% of treated patients, approximately 24%. The Adverse events section identifies neutralizing antibodies that inhibited enzyme activity in vitro in one patient, but does not say that all four antibody-positive patients had neutralizing antibodies. The claim incorrectly applies the 24% figure to neutralizing antibodies. (LLM, conf=0.91)
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Research works printed but not linked: 21
- Grabowski GA. Gaucher disease. Enzymology, genetics, and treatment. Adv Hum Genet 1993;21:377-441.
- Cox TM, Schofield JP. Gaucher's disease: Clinical features and natural history. Baillieres Clin Haematol 1997;10:657-689.
- Grabowski GA, Barton NW, Pastores G, et al. Enzyme therapy in type 1 Gaucher disease: Comparative efficacy of mannose-terminated glucocerebrosidase from natural and recombinant sources. Ann Intern Med 1995;122:33-39.
- Brumshtein B, Salinas P, Peterson B, et al. Characterization of gene-activated human acid-beta-glucosidase: Crystal structure, glycan composition, and internalization into macrophages. Glycobiology 2010;20:24-32.
- Takasaki S, Murray GJ, Furbish FS, et al. Structure of the N-asparagine-linked oligosaccharide units of human placental beta-glucocerebrosidase. J Biol Chem 1984;259:10112-10117.
- Zimran A, Altarescu G, Philips M, et al. Phase 1/2 and extension study of velaglucerase alfa replacement therapy in adults with type 1 Gaucher disease: 48-month experience. Blood 2010;115:4651-4656.
- Aguilera B, Ghauharali-van der Vlugt K, Helmond MT, et al. Transglycosidase activity of chitotriosidase: Improved enzymatic assay for the human macrophage chitinase. J Biol Chem 2003;278:40911-40916.
- Schoonhoven A, Rudensky B, Elstein D, et al. Monitoring of Gaucher patients with a novel chitotriosidase assay. Clin Chim Acta 2007;381:136-139.
- Boot RG, Verhoek M, de Fost M, et al. Marked elevation of the chemokine CCL18/PARC in Gaucher disease: A novel surrogate marker for assessing therapeutic intervention. Blood 2004;103:33-39.
- Sellos-Moura M, Barzegar S, Pan L, et al. Development of a panel of highly sensitive, equivalent assays for detection of antibody responses to velaglucerase alfa or imiglucerase enzyme replacement therapy in patients with Gaucher disease. J Immunol Methods 2011;373:45-53.
- Ludwig J. Current Methods of Autopsy Practice. Philadelphia: W. B. Saunders; 1979. pp 676-685.
- Hill SC, Damaska BM, Ling A, et al. Gaucher disease: Abdominal MR imaging findings in 46 patients. Radiology 1992;184:561-566.
- Stein P, Malhotra A, Haims A, et al. Focal splenic lesions in type I Gaucher disease are associated with poor platelet and splenic response to macrophage-targeted enzyme replacement therapy. J Inherit Metab Dis 2010;33:769-774.
- Goker-Alpan O, Hruska KS, Orvisky E, et al. Divergent phenotypes in Gaucher disease implicate the role of modifiers. J Med Genet 2005;42:e37.
- Ida H, Rennert OM, Iwasawa K, et al. Clinical and genetic studies of Japanese homozygotes for the Gaucher disease L444P mutation. Hum Genet 1999;105:120-126.
- Patterson MC, Horowitz M, Abel RB, et al. Isolated horizontal supranuclear gaze palsy as a marker of severe systemic involvement in Gaucher's disease. Neurology 1993;43:1993-1997.
- Altarescu G, Hill S, Wiggs E, et al. The efficacy of enzyme replacement therapy in patients with chronic neuronopathic Gaucher's disease. J Pediatr 2001;138:539-547.
- Starzyk K, Richards S, Yee J, et al. The long-term international safety experience of imiglucerase therapy for Gaucher disease. Mol Genet Metab 2007;90:157-163.
- Rosenberg M, Kingma W, Fitzpatrick MA, et al. Immunosurveillance of alglucerase enzyme therapy for Gaucher patients: Induction of humoral tolerance in seroconverted patients after repeat administration. Blood 1999;93:2081-2088.
- Hollak CE, vom Dahl S, Aerts JM, et al. Force majeure: Therapeutic measures in response to restricted supply of imiglucerase (Cerezyme) for patients with Gaucher disease. Blood Cells Mol Dis 2010;44:41-47.
- Sirrs S. The Fabrazyme shortage-A call to action for metabolic physicians. Mol Genet Metab 2010;102:4-5. Figure
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Therapeutic glycoprotein production in mammalian cells
Lalonde, M.-E., & Durocher, Y. (2017) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2017.04.028 · Cited by 296 · see citing works
- Authors
- Turkia, H. B., Gonzalez, D. E., Barton, N. W., Zimran, A., Kabra, M., Lukina, E. A., Giraldo, P., Kisinovsky, I., Bavdekar, A., Dridi, M. B., Gupta, N., Kishnani, P. S., Sureshkumar, E. K., Wang, N., Crombez, E., Bhirangi, K., & Mehta, A.
- Affiliations
- Hôpital La Rabta (TN)
- Sanatorio Español Asunción Paraguay
- Takeda (United States) (US)
- Shaare Zedek Medical Center (IL)
- All India Institute of Medical Sciences (IN)
- National Medical Research Center for Hematology (RU)
- Centre for Biomedical Network Research on Rare Diseases (ES)
- Your Health S. A. Buenos Aires Argentina
- KEM Hospital Research Centre Pune India
- Duke Medical Center (US)
- Malabar Institute of Medical Sciences (IN)
- The Royal Free Hospital (GB)
- Corresponding author
- Mehta, Atul
- ORCID
- Venue
- American Journal of Hematology
- Publisher
- Wiley
- Published
- 2013-02-09
- Volume
- 88
- Issue
- 3
- Pages
- 179-184
- ISSN
- 0361-8609 (ISSN-L)
- 1096-8652
- OpenAlex
- W1987406270
- Cited by
- 71
- References
- 0
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 3 · 2023: 1 · 2022: 5 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 3 · 2017: 4 · 2016: 7 · 2015: 13 · 2014: 7 · 2013: 6
- FWCI
- 5.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Hematology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- Amicus Therapeutics
- Topics
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- Gaucher disease type 1, velaglucerase alfa, imiglucerase, enzyme replacement therapy, non-inferiority, hemoglobin levels, anemia, immunogenicity, anti-drug antibodies, splenectomy, pediatric patients, organomegaly, thrombocytopenia
- MeSH terms
- Adolescent, Adult, Aged, Antibodies, Child, Child, Preschool, Double-Blind Method, Drug Administration Schedule, Female, Gaucher Disease, Glucosylceramidase, Hemoglobins, Humans, Injections, Intravenous, Male, Middle Aged, Platelet Count, Recombinant Proteins, Splenectomy, Treatment Outcome, Enzyme Replacement Therapy
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