ArticleMolecular genetics and metabolism
Successful within-patient dose escalation of olipudase alfa in acid sphingomyelinase deficiency.
Article in Molecular genetics and metabolism. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.
- Consensus clinical management guidelines for acid sphingomyelinase deficiency (Niemann-Pick disease types A, B and A/B).Orphanet journal of rare diseases · 2023Guideline
- Adults With Acid Sphingomyelinase Deficiency Have Sustained Improvements in Clinical Outcomes With up to 5 Years of Olipudase Alfa Enzyme Replacement Therapy: ASCEND Trial Final Results.Journal of inherited metabolic disease · 2026Trial
- Long-Term Safety and Clinical Outcomes With Olipudase Alfa Enzyme Replacement Therapy in Children and Adolescents With Acid Sphingomyelinase Deficiency.Journal of inherited metabolic disease · 2025Trial
- One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Trial
- Olipudase alfa for treatment of acid sphingomyelinase deficiency (ASMD): safety and efficacy in adults treated for 30 months.Journal of inherited metabolic disease · 2018Trial
- Targeting of Acid Sphingomyelinase, a Lysosomal Membrane Protein, Using Apolipoprotein E3-containing Nanodiscs.The Journal of membrane biology · 2026Article
- Acid Sphingomyelinase Activity in Dried Blood Spot from Neonatal Intensive Care Unit-Admitted Neonates: A Pilot Study for Expanded Newborn Screening in Japan.International journal of neonatal screening · 2026Article
- Olipudase alfa treatment for pediatric acid sphingomyelinase deficiency in Egypt: A prospective, observational cohort study with an interventional subgroup.Molecular genetics and metabolism reports · 2026Article
- Review
- From Genes to Treatment: Literature Review and Perspectives on Acid Sphingomyelinase Deficiency in Children.Diagnostics (Basel, Switzerland) · 2025Review
- The Genetic Basis, Lung Involvement, and Therapeutic Options in Niemann-Pick Disease: A Comprehensive Review.Biomolecules · 2024Review
- The impact of sphingomyelin on the pathophysiology and treatment response to olipudase alfa in acid sphingomyelinase deficiency.Genetics in medicine open · 2024Review
- Continued improvement in disease manifestations of acid sphingomyelinase deficiency for adults with up to 2 years of olipudase alfa treatment: open-label extension of the ASCEND trial.Orphanet journal of rare diseases · 2023Article
- Clinical and biochemical footprints of inherited metabolic diseases. XIII. Respiratory manifestations.Molecular genetics and metabolism · 2023Review
- Review
- Polymer-based drug delivery systems under investigation for enzyme replacement and other therapies of lysosomal storage disorders.Advanced drug delivery reviews · 2023Review
- Perspectives of Rare Disease Experts on Newborn Genome Sequencing.JAMA network open · 2023Article
- Olipudase Alfa in Non-CNS Manifestations of Acid Sphingomyelinase Deficiency: A Profile of Its Use.Clinical drug investigation · 2023Review
- 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 · 2023Article
- Sphingomyelin 16:0 is a therapeutic target for neuronal death in acid sphingomyelinase deficiency.Cell death & disease · 2023Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundOlipudase alfa, a recombinant human acid sphingomyelinase (rhASM), is an investigational enzyme replacement therapy (ERT) for patients with ASM deficiency [ASMD; Niemann-Pick Disease (NPD) A and B]. This open-label phase 1b study assessed the safety and tolerability of olipudase alfa using within-patient dose escalation to gradually debulk accumulated sphingomyelin and mitigate the rapid production of metabolites, which can be toxic. Secondary objectives were pharmacokinetics, pharmacodynamics, and exploratory efficacy.
methodsFive adults with nonneuronopathic ASMD (NPD B) received escalating doses (0.1 to 3.0 mg/kg) of olipudase alfa intravenously every 2 weeks for 26 weeks.
resultsAll patients successfully reached 3.0mg/kg without serious or severe adverse events. One patient repeated a dose (2.0 mg/kg) and another had a temporary dose reduction (1.0 to 0.6 mg/kg). Most adverse events (97%) were mild and all resolved without sequelae. The most common adverse events were headache, arthralgia, nausea and abdominal pain. Two patients experienced single acute phase reactions. No patient developed hypersensitivity or anti-olipudase alfa antibodies. The mean circulating half-life of olipudase alfa ranged from 20.9 to 23.4h across doses without accumulation. Ceramide, a sphingomyelin catabolite, rose transiently in plasma after each dose, but decreased over time. Reductions in sphingomyelin storage, spleen and liver volumes, and serum chitotriosidase activity, as well as improvements in infiltrative lung disease, lipid profiles, platelet counts, and quality of life assessments, were observed.
conclusionsThis study provides proof-of-concept for the safety and efficacy of within-patient dose escalation of olipudase alfa in patients with nonneuronopathic ASMD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.