One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency

Genet Med. 2021 Aug;23(8):1543-1550. doi: 10.1038/s41436-021-01156-3. Epub 2021 Apr 19.


Purpose: To assess olipudase alfa enzyme replacement therapy for non-central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in children.

Methods: This phase 1/2, international, multicenter, open-label trial (ASCEND-Peds/NCT02292654) administered intravenous olipudase alfa every 2 weeks with intrapatient dose escalation to 3 mg/kg. Primary outcome was safety through week 64. Secondary outcomes included pharmacokinetics, spleen and liver volumes, lung diffusing capacity (DLCO), lipid profiles, and height through week 52.

Results: Twenty patients were enrolled: four adolescents (12-17 years), nine children (6-11 years), and seven infants/early child (1-5 years). Most adverse events were mild or moderate, including infusion-associated reactions (primarily urticaria, pyrexia, and/or vomiting) in 11 patients. Three patients had serious treatment-related events: one with transient asymptomatic alanine aminotransferase increases, another with urticaria and rash (antidrug antibody positive [ADA+]), and a third with an anaphylactic reaction (ADA+) who underwent desensitization and reached the 3 mg/kg maintenance dose. Mean splenomegaly and hepatomegaly improved by >40% (p < 0.0001). Mean % predicted DLCO improved by 32.9% (p = 0.0053) in patients able to perform the test. Lipid profiles and elevated liver transaminase levels normalized. Mean height Z-scores improved by 0.56 (p < 0.0001).

Conclusion: In this study in children with chronic ASMD, olipudase alfa was generally well-tolerated with significant, comprehensive improvements in disease pathology across a range of clinically relevant endpoints.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Enzyme Replacement Therapy
  • Humans
  • Infant
  • Liver
  • Niemann-Pick Disease, Type A* / drug therapy
  • Niemann-Pick Disease, Type A* / genetics
  • Recombinant Proteins / therapeutic use
  • Sphingomyelin Phosphodiesterase / genetics


  • Recombinant Proteins
  • Sphingomyelin Phosphodiesterase
  • olipudase alfa

Associated data