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Long-term velaglucerase alfa treatment in children with Gaucher disease type 1 naïve to enzyme replacement therapy or previously treated with imiglucerase.
Mol Genet Metab. 2016 Feb; 117(2):164-71.MG

Abstract

BACKGROUND

Gaucher Disease type 1 (GD1) often manifests in childhood. Early treatment with enzyme replacement therapy (ERT) may prevent disease complications. We report the assessment of velaglucerase alfa ERT in pediatric GD1 patients who participated in a long-term extension study (HGT-GCB-044, ClinicalTrials.gov Identifier NCT00635427).

METHODS

Safety and efficacy were evaluated in pediatric patients receiving velaglucerase alfa 30-60U/kg by intravenous infusion every other week. In addition to key hematological and visceral efficacy assessments, exploratory assessments conducted specifically in pediatric patients included evaluation of height, bone age, bone marrow burden, and Tanner stage of puberty.

RESULTS

The study included 24 pediatric patients. Fifteen patients were naïve to ERT on entry into the preceding trials TKT032 (12-month trial) or HGT-GCB-039 (9-month trial): in the preceding trials, ten of these 15 patients received velaglucerase alfa and five patients received imiglucerase ERT. Nine patients in the study were previously treated with imiglucerase for >30months and were switched to velaglucerase alfa in the preceding trial TKT034 (12-month trial). Cumulative ERT exposure in the clinical studies ranged from 2.0 to 5.8years. Three serious adverse events, including a fatal convulsion, were reported; none were deemed related to velaglucerase alfa. One patient tested positive for anti-velaglucerase alfa antibodies. An efficacy assessment at 24months showed that velaglucerase alfa had positive effects on primary hematological and visceral parameters in treatment-naïve patients, which were maintained with longer-term treatment. Disease parameters were stable in patients switched from long-term imiglucerase ERT. Exploratory results may suggest benefits of early treatment to enable normal growth in pediatric patients.

CONCLUSION

The safety profile and clinical response seen in pediatric patients are consistent with results reported in adults.

Authors+Show Affiliations

Center for Pediatric Genomic Medicine, Children's Mercy-Kansas City, 2401 Gillham Road, Kansas City, MO 64108, USA. Electronic address: ldsmith@cmh.edu.Children's Hospital of Wisconsin, Milwaukee, WI, USA.Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.Department of Human Genetics, Division of Medical Genetics, School of Medicine, Emory University, Atlanta, GA, USA; Department of Ophthalmology, School of Medicine, Emory University, Atlanta, GA, USA.Pediatric Gastroenterology Department, King Edward Memorial Hospital Research Centre, Pune, India.Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.Kaiser Permanente, Los Angeles, CA, USA.Department of Gastroenterology, Hepatology, and Nutrition, UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA.Department of Biomedical, Industrial, & Human Factors Engineering, Wright State University, Dayton, OH, USA.Biostatistics & Statistical Programming Department, Shire, Lexington, MA, USA.Rare Disease Unit, Shire, Lexington, MA, USA.Department of Medicine/National Centre for Inherited Metabolic Disorders, Mater Misericordiae University Hospital, Dublin, Ireland.

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

26043810

Citation

Smith, Laurie, et al. "Long-term Velaglucerase Alfa Treatment in Children With Gaucher Disease Type 1 Naïve to Enzyme Replacement Therapy or Previously Treated With Imiglucerase." Molecular Genetics and Metabolism, vol. 117, no. 2, 2016, pp. 164-71.
Smith L, Rhead W, Charrow J, et al. Long-term velaglucerase alfa treatment in children with Gaucher disease type 1 naïve to enzyme replacement therapy or previously treated with imiglucerase. Mol Genet Metab. 2016;117(2):164-71.
Smith, L., Rhead, W., Charrow, J., Shankar, S. P., Bavdekar, A., Longo, N., Mardach, R., Harmatz, P., Hangartner, T., Lee, H. M., Crombez, E., & Pastores, G. M. (2016). Long-term velaglucerase alfa treatment in children with Gaucher disease type 1 naïve to enzyme replacement therapy or previously treated with imiglucerase. Molecular Genetics and Metabolism, 117(2), 164-71. https://doi.org/10.1016/j.ymgme.2015.05.012
Smith L, et al. Long-term Velaglucerase Alfa Treatment in Children With Gaucher Disease Type 1 Naïve to Enzyme Replacement Therapy or Previously Treated With Imiglucerase. Mol Genet Metab. 2016;117(2):164-71. PubMed PMID: 26043810.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-term velaglucerase alfa treatment in children with Gaucher disease type 1 naïve to enzyme replacement therapy or previously treated with imiglucerase. AU - Smith,Laurie, AU - Rhead,William, AU - Charrow,Joel, AU - Shankar,Suma P, AU - Bavdekar,Ashish, AU - Longo,Nicola, AU - Mardach,Rebecca, AU - Harmatz,Paul, AU - Hangartner,Thomas, AU - Lee,Hak-Myung, AU - Crombez,Eric, AU - Pastores,Gregory M, Y1 - 2015/06/01/ PY - 2015/03/10/received PY - 2015/05/21/revised PY - 2015/05/21/accepted PY - 2015/6/6/entrez PY - 2015/6/6/pubmed PY - 2016/11/4/medline KW - Children and adolescents KW - Enzyme replacement therapy KW - Gaucher disease KW - Pediatric patients KW - Velaglucerase alfa SP - 164 EP - 71 JF - Molecular genetics and metabolism JO - Mol. Genet. Metab. VL - 117 IS - 2 N2 - BACKGROUND: Gaucher Disease type 1 (GD1) often manifests in childhood. Early treatment with enzyme replacement therapy (ERT) may prevent disease complications. We report the assessment of velaglucerase alfa ERT in pediatric GD1 patients who participated in a long-term extension study (HGT-GCB-044, ClinicalTrials.gov Identifier NCT00635427). METHODS: Safety and efficacy were evaluated in pediatric patients receiving velaglucerase alfa 30-60U/kg by intravenous infusion every other week. In addition to key hematological and visceral efficacy assessments, exploratory assessments conducted specifically in pediatric patients included evaluation of height, bone age, bone marrow burden, and Tanner stage of puberty. RESULTS: The study included 24 pediatric patients. Fifteen patients were naïve to ERT on entry into the preceding trials TKT032 (12-month trial) or HGT-GCB-039 (9-month trial): in the preceding trials, ten of these 15 patients received velaglucerase alfa and five patients received imiglucerase ERT. Nine patients in the study were previously treated with imiglucerase for >30months and were switched to velaglucerase alfa in the preceding trial TKT034 (12-month trial). Cumulative ERT exposure in the clinical studies ranged from 2.0 to 5.8years. Three serious adverse events, including a fatal convulsion, were reported; none were deemed related to velaglucerase alfa. One patient tested positive for anti-velaglucerase alfa antibodies. An efficacy assessment at 24months showed that velaglucerase alfa had positive effects on primary hematological and visceral parameters in treatment-naïve patients, which were maintained with longer-term treatment. Disease parameters were stable in patients switched from long-term imiglucerase ERT. Exploratory results may suggest benefits of early treatment to enable normal growth in pediatric patients. CONCLUSION: The safety profile and clinical response seen in pediatric patients are consistent with results reported in adults. SN - 1096-7206 UR - https://www.unboundmedicine.com/medline/citation/26043810/Long_term_velaglucerase_alfa_treatment_in_children_with_Gaucher_disease_type_1_naïve_to_enzyme_replacement_therapy_or_previously_treated_with_imiglucerase_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1096-7192(15)30017-2 DB - PRIME DP - Unbound Medicine ER -