One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency.
Genet Med
; 23(8): 1543-1550, 2021 08.
Article
in En
| MEDLINE
| ID: mdl-33875845
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Niemann-Pick Disease, Type A
Type of study:
Clinical_trials
/
Prognostic_studies
Limits:
Adolescent
/
Child
/
Child, preschool
/
Humans
/
Infant
Language:
En
Journal:
Genet Med
Journal subject:
GENETICA MEDICA
Year:
2021
Document type:
Article
Affiliation country:
Estados Unidos