Tags

Type your tag names separated by a space and hit enter

Olipudase alfa enzyme replacement therapy for acid sphingomyelinase deficiency (ASMD): sustained improvements in clinical outcomes after 6.5 years of treatment in adults.
Orphanet J Rare Dis. 2023 04 25; 18(1):94.OJ

Abstract

BACKGROUND

Enzyme replacement therapy with olipudase alfa, a recombinant human acid sphingomyelinase (rhASM), is indicated for non-central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in children and adults. An ongoing, open-label, long-term study (NCT02004704) assessed the safety and efficacy of olipudase alfa in 5 adults with ASMD.

RESULTS

After 6.5 years of treatment, there were no discontinuations, no olipudase-alfa-related serious adverse events, and no new safety signals compared to earlier assessments. Most treatment-emergent adverse events were mild in intensity (1742/1766, 98.6%). Among treatment-related adverse events (n = 657), more than half were considered infusion-associated reactions (n = 403, 61.3%) such as headache, nausea, abdominal pain, arthralgia, pyrexia, and fatigue. No patient developed neutralizing anti-drug antibodies to cellular uptake, and there were no clinically significant adverse changes in vital signs, hematology, or cardiac safety parameters. Improvements (decreases) in spleen and liver volumes progressed through 6.5 years (mean changes from baseline of -59.5% and -43.7%, respectively). There was a mean increase in diffusing capacity of the lung for carbon monoxide from baseline of 55.3%, accompanied by improvements in interstitial lung disease parameters. Lipid profiles at baseline indicated dyslipidemia. All patients had sustained decreases in pro-atherogenic lipid levels and increases in anti-atherogenic lipid levels following olipudase alfa treatment.

CONCLUSIONS

Olipudase alfa is the first disease-specific treatment for ASMD. This study demonstrates that long-term treatment with olipudase alfa is well-tolerated and is associated with sustained improvements in relevant disease clinical measures. NCT02004704 registered 26 November 2013, https://clinicaltrials.gov/ct2/show/NCT02004704?term=NCT02004704&draw=2&rank=1 .

Links

PMC Free PDF

Authors+Show Affiliations

Lachmann RH
National Hospital for Neurology, University College London Hospitals, London, UK. r.lachmann@nhs.net.
Diaz GA
Icahn School of Medicine at Mount Sinai, New York, NY, US.
Wasserstein MP
Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, US.
Armstrong NM
Sanofi, Cambridge, MA, USA.
Yarramaneni A
Sanofi, Bridgewater, NJ, USA.
Kim Y
Sanofi, Paris, France.
Kumar M
Sanofi, Bridgewater, NJ, USA.

MeSH

AdultHumansEnzyme Replacement TherapyLipidsNiemann-Pick Disease, Type ANiemann-Pick DiseasesSphingomyelin Phosphodiesterase

Pub Type(s)

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

Language

eng

PubMed ID

37098529

Citation

Lachmann, Robin H., et al. "Olipudase Alfa Enzyme Replacement Therapy for Acid Sphingomyelinase Deficiency (ASMD): Sustained Improvements in Clinical Outcomes After 6.5 Years of Treatment in Adults." Orphanet Journal of Rare Diseases, vol. 18, no. 1, 2023, p. 94.
Lachmann RH, Diaz GA, Wasserstein MP, et al. Olipudase alfa enzyme replacement therapy for acid sphingomyelinase deficiency (ASMD): sustained improvements in clinical outcomes after 6.5 years of treatment in adults. Orphanet J Rare Dis. 2023;18(1):94.
Lachmann, R. H., Diaz, G. A., Wasserstein, M. P., Armstrong, N. M., Yarramaneni, A., Kim, Y., & Kumar, M. (2023). Olipudase alfa enzyme replacement therapy for acid sphingomyelinase deficiency (ASMD): sustained improvements in clinical outcomes after 6.5 years of treatment in adults. Orphanet Journal of Rare Diseases, 18(1), 94. https://doi.org/10.1186/s13023-023-02700-x
Lachmann RH, et al. Olipudase Alfa Enzyme Replacement Therapy for Acid Sphingomyelinase Deficiency (ASMD): Sustained Improvements in Clinical Outcomes After 6.5 Years of Treatment in Adults. Orphanet J Rare Dis. 2023 04 25;18(1):94. PubMed PMID: 37098529.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Olipudase alfa enzyme replacement therapy for acid sphingomyelinase deficiency (ASMD): sustained improvements in clinical outcomes after 6.5 years of treatment in adults. AU - Lachmann,Robin H, AU - Diaz,George A, AU - Wasserstein,Melissa P, AU - Armstrong,Nicole M, AU - Yarramaneni,Abhimanyu, AU - Kim,Yong, AU - Kumar,Monica, Y1 - 2023/04/25/ PY - 2022/12/14/received PY - 2023/04/06/accepted PY - 2023/4/27/medline PY - 2023/4/26/pubmed PY - 2023/4/25/entrez KW - Acid sphingomyelinase deficiency KW - Niemann-Pick disease type B and type A/B KW - Olipudase alfa KW - Recombinant human acid sphingomyelinase SP - 94 EP - 94 JF - Orphanet journal of rare diseases JO - Orphanet J Rare Dis VL - 18 IS - 1 N2 - BACKGROUND: Enzyme replacement therapy with olipudase alfa, a recombinant human acid sphingomyelinase (rhASM), is indicated for non-central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in children and adults. An ongoing, open-label, long-term study (NCT02004704) assessed the safety and efficacy of olipudase alfa in 5 adults with ASMD. RESULTS: After 6.5 years of treatment, there were no discontinuations, no olipudase-alfa-related serious adverse events, and no new safety signals compared to earlier assessments. Most treatment-emergent adverse events were mild in intensity (1742/1766, 98.6%). Among treatment-related adverse events (n = 657), more than half were considered infusion-associated reactions (n = 403, 61.3%) such as headache, nausea, abdominal pain, arthralgia, pyrexia, and fatigue. No patient developed neutralizing anti-drug antibodies to cellular uptake, and there were no clinically significant adverse changes in vital signs, hematology, or cardiac safety parameters. Improvements (decreases) in spleen and liver volumes progressed through 6.5 years (mean changes from baseline of -59.5% and -43.7%, respectively). There was a mean increase in diffusing capacity of the lung for carbon monoxide from baseline of 55.3%, accompanied by improvements in interstitial lung disease parameters. Lipid profiles at baseline indicated dyslipidemia. All patients had sustained decreases in pro-atherogenic lipid levels and increases in anti-atherogenic lipid levels following olipudase alfa treatment. CONCLUSIONS: Olipudase alfa is the first disease-specific treatment for ASMD. This study demonstrates that long-term treatment with olipudase alfa is well-tolerated and is associated with sustained improvements in relevant disease clinical measures. NCT02004704 registered 26 November 2013, https://clinicaltrials.gov/ct2/show/NCT02004704?term=NCT02004704&draw=2&rank=1 . SN - 1750-1172 UR - https://www.unboundmedicine.com/medline/citation/37098529/Olipudase_alfa_enzyme_replacement_therapy_for_acid_sphingomyelinase_deficiency__ASMD_:_sustained_improvements_in_clinical_outcomes_after_6_5_years_of_treatment_in_adults_ DB - PRIME DP - Unbound Medicine ER -