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Long-term safety and clinical outcomes of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency: two-year results.
Orphanet J Rare Dis. 2022 12 14; 17(1):437.OJ

Abstract

BACKGROUND

Olipudase alfa is a recombinant human acid sphingomyelinase (ASM) enzyme replacement therapy (ERT) for non-central-nervous-system manifestations of acid sphingomyelinase deficiency (ASMD). We report 2-year cumulative safety and efficacy data after olipudase alfa treatment in 20 children (four adolescents [12-17 year], nine children [6-11 year], and seven infants/early child [1-5 year]) with baseline splenomegaly and growth deficits who completed the 1-year ASCEND-Peds clinical trial (NCT02292654) and who continue to receive olipudase alfa in a long-term study (NCT02004704). Efficacy endpoints include spleen and liver volumes, diffusing capacity of the lung for carbon monoxide (DLCO), high-resolution computed tomography (HRCT) lung imaging, lipid profiles, liver function tests, and height Z-scores.

RESULTS

All 20 former ASCEND-Peds patients completed at least 2 years of olipudase alfa treatment. No patient discontinued and no new safety issue arose during the second year of treatment; 99% of adverse events were mild or moderate. During year 2, one patient had two treatment-related serious events of hypersensitivity that resolved. Mean reductions from baseline in spleen and liver volumes were 61% and 49%, respectively (p < 0.0001) and mean percent-predicted-DLCO increased by 46.6% (p < 0.0001) in nine patients who performed the test at baseline. Lipid profiles and elevated liver transaminase levels that improved or normalized by 1 year remained stable. Mean height Z-scores improved in all age groups (mean change from baseline 1.17, P < 0.0001).

CONCLUSION

Olipudase alfa was generally well-tolerated during 2 years of treatment. Improvements in clinically relevant disease endpoints observed during the first year of treatment were maintained or augmented in the second year. Trial registration NCT02004704 registered 26 Nov 2013, https://clinicaltrials.gov/ct2/show/record/NCT02004704 .

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Authors+Show Affiliations

Diaz GA
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA. george.diaz@mssm.edu.
Giugliani R
Medical Genetics Service HCPA, Department of Genetics UFRGS, DASA and Casa dos Raros, Porto Alegre, Brazil.
Guffon N
Reference Centre of Inherited Metabolic Disease in Femme Mère Enfant Hospital, Hospices Civils of Lyon, Lyon, France.
Jones SA
Manchester University National Health Service Trust, St Mary's Hospital, Manchester, UK.
Mengel E
Institute of Clinical Science for Lysosomal Storage Disorders, SphinCS GmbH, Mainz, Germany.
Scarpa M
University Hospital of Udine, Udine, Italy.
Witters P
University Hospitals Leuven, Leuven, Belgium.
Yarramaneni A
Sanofi, Bridgewater, NJ, USA.
Li J
Sanofi, Bridgewater, NJ, USA.
Armstrong NM
Sanofi, Cambridge, MA, USA.
Kim Y
Sanofi, Paris, France.
Ortemann-Renon C
Sanofi, Bridgewater, NJ, USA.
Kumar M
Sanofi, Bridgewater, NJ, USA.

MeSH

AdolescentHumansChildNiemann-Pick Disease, Type ASphingomyelin PhosphodiesteraseEnzyme Replacement TherapyNiemann-Pick DiseasesLipids

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

36517856

Citation

Diaz, George A., et al. "Long-term Safety and Clinical Outcomes of Olipudase Alfa Enzyme Replacement Therapy in Pediatric Patients With Acid Sphingomyelinase Deficiency: Two-year Results." Orphanet Journal of Rare Diseases, vol. 17, no. 1, 2022, p. 437.
Diaz GA, Giugliani R, Guffon N, et al. Long-term safety and clinical outcomes of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency: two-year results. Orphanet J Rare Dis. 2022;17(1):437.
Diaz, G. A., Giugliani, R., Guffon, N., Jones, S. A., Mengel, E., Scarpa, M., Witters, P., Yarramaneni, A., Li, J., Armstrong, N. M., Kim, Y., Ortemann-Renon, C., & Kumar, M. (2022). Long-term safety and clinical outcomes of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency: two-year results. Orphanet Journal of Rare Diseases, 17(1), 437. https://doi.org/10.1186/s13023-022-02587-0
Diaz GA, et al. Long-term Safety and Clinical Outcomes of Olipudase Alfa Enzyme Replacement Therapy in Pediatric Patients With Acid Sphingomyelinase Deficiency: Two-year Results. Orphanet J Rare Dis. 2022 12 14;17(1):437. PubMed PMID: 36517856.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-term safety and clinical outcomes of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency: two-year results. AU - Diaz,George A, AU - Giugliani,Roberto, AU - Guffon,Nathalie, AU - Jones,Simon A, AU - Mengel,Eugen, AU - Scarpa,Maurizio, AU - Witters,Peter, AU - Yarramaneni,Abhimanyu, AU - Li,Jing, AU - Armstrong,Nicole M, AU - Kim,Yong, AU - Ortemann-Renon,Catherine, AU - Kumar,Monica, Y1 - 2022/12/14/ PY - 2022/06/27/received PY - 2022/11/22/accepted PY - 2022/12/14/entrez PY - 2022/12/15/pubmed PY - 2022/12/17/medline KW - Acid sphingomyelinase deficiency KW - Dose escalation KW - Lung diffusing capacity KW - Niemann–Pick type B KW - Organomegaly KW - Recombinant human acid sphingomyelinase SP - 437 EP - 437 JF - Orphanet journal of rare diseases JO - Orphanet J Rare Dis VL - 17 IS - 1 N2 - BACKGROUND: Olipudase alfa is a recombinant human acid sphingomyelinase (ASM) enzyme replacement therapy (ERT) for non-central-nervous-system manifestations of acid sphingomyelinase deficiency (ASMD). We report 2-year cumulative safety and efficacy data after olipudase alfa treatment in 20 children (four adolescents [12-17 year], nine children [6-11 year], and seven infants/early child [1-5 year]) with baseline splenomegaly and growth deficits who completed the 1-year ASCEND-Peds clinical trial (NCT02292654) and who continue to receive olipudase alfa in a long-term study (NCT02004704). Efficacy endpoints include spleen and liver volumes, diffusing capacity of the lung for carbon monoxide (DLCO), high-resolution computed tomography (HRCT) lung imaging, lipid profiles, liver function tests, and height Z-scores. RESULTS: All 20 former ASCEND-Peds patients completed at least 2 years of olipudase alfa treatment. No patient discontinued and no new safety issue arose during the second year of treatment; 99% of adverse events were mild or moderate. During year 2, one patient had two treatment-related serious events of hypersensitivity that resolved. Mean reductions from baseline in spleen and liver volumes were 61% and 49%, respectively (p < 0.0001) and mean percent-predicted-DLCO increased by 46.6% (p < 0.0001) in nine patients who performed the test at baseline. Lipid profiles and elevated liver transaminase levels that improved or normalized by 1 year remained stable. Mean height Z-scores improved in all age groups (mean change from baseline 1.17, P < 0.0001). CONCLUSION: Olipudase alfa was generally well-tolerated during 2 years of treatment. Improvements in clinically relevant disease endpoints observed during the first year of treatment were maintained or augmented in the second year. Trial registration NCT02004704 registered 26 Nov 2013, https://clinicaltrials.gov/ct2/show/record/NCT02004704 . SN - 1750-1172 UR - https://www.unboundmedicine.com/medline/citation/36517856/Long_term_safety_and_clinical_outcomes_of_olipudase_alfa_enzyme_replacement_therapy_in_pediatric_patients_with_acid_sphingomyelinase_deficiency:_two_year_results_ DB - PRIME DP - Unbound Medicine ER -
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