Clinical outcomes after long-term treatment with alglucosidase alfa in infants and children with advanced Pompe disease.
OBJECTIVE
A clinical trial was conducted to evaluate the safety and efficacy of alglucosidase alfa in infants and children with advanced Pompe disease.


METHODS
Open-label, multicenter study of IV alglucosidase alfa treatment in 21 infants 3-43 months old (median 13 months) with minimal acid alpha-glucosidase activity and abnormal left ventricular mass index by echocardiography. Patients received IV alglucosidase alfa every 2 weeks for up to 168 weeks (median 120 weeks). Survival results were compared with an untreated reference cohort.


RESULTS
At study end, 71% (15/21) of patients were alive and 44% (7/16) of invasive-ventilator free patients remained so. Compared with the untreated reference cohort, alglucosidase alfa reduced the risk of death by 79% (P < 0.001) and the risk of invasive ventilation by 58% (P = 0.02). Left ventricular mass index improved or remained normal in all patients evaluated beyond 12 weeks; 62% (13/21) achieved new motor milestones. Five patients were walking independently at the end of the study and 86% (18/21) gained functional independence skills. Overall, 52% (11/21) of patients experienced infusion-associated reactions; 95% (19/20) developed IgG antibodies to recombinant human lysosomal acid alpha-glucosidase; no patients withdrew from the study because of safety concerns.


CONCLUSIONS
In this population of infants with advanced disease, biweekly infusions with alglucosidase alfa prolonged survival and invasive ventilation-free survival. Treatment also improved indices of cardiomyopathy, motor skills, and functional independence.
Nicolino
Marc
M
Division of Pediatric Endocrinology, Diabetology and Metabolism, Hôpital Debrousse, University Lyon, Lyon, France.
Byrne
Barry
B
Wraith
J Edmund
JE
Leslie
Nancy
N
Mandel
Hanna
H
Freyer
David R
DR
Arnold
Georgianne L
GL
Pivnick
Eniko K
EK
Ottinger
C J
CJ
Robinson
Peter H
PH
Loo
John-Charles A
JC
Smitka
Martin
M
Jardine
Philip
P
Tatò
Luciano
L
Chabrol
Brigitte
B
McCandless
Shawn
S
Kimura
Shigemi
S
Mehta
L
L
Bali
Deeksha
D
Skrinar
Alison
A
Morgan
Claire
C
Rangachari
Lakshmi
L
Corzo
Deya
D
Kishnani
Priya S
PS
D001827:Body Height; D001835:Body Weight; D002675:Child, Preschool; D003371:Cough / Q000139:chemically induced; D004452:Echocardiography; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006003:Glycogen / Q000378:metabolism; D006009:Glycogen Storage Disease Type II / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D012871:Skin Diseases / Q000139:chemically induced; D013997:Time Factors; D016896:Treatment Outcome; D000520:alpha-Glucosidases / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*
D007074:Immunoglobulin G; D006003:Glycogen; C509951:GAA protein, human; D000520:alpha-Glucosidases