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

Abstract

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.

• Authors: George A Diaz, Simon A Jones, Maurizio Scarpa, Karl Eugen Mengel, Roberto Giugliani, Nathalie Guffon, Isabela Batsu, Patricia A Fraser, Jing Li, Qi Zhang, Catherine Ortemann-Renon
• Journal: Genetics in medicine : official journal of the American College of Medical Genetics (Genet Med) Vol. 23 Issue 8 Pg. 1543-1550 (08 2021) ISSN: 1530-0366 [Electronic] United States
• PMID: 33875845 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• Recombinant Proteins
• Sphingomyelin Phosphodiesterase
• olipudase alfa

Topics

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