Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in infantile-onset Pompe disease.
OBJECTIVE
To conduct an open-label, multinational, multicenter study examining the safety and efficacy of recombinant human acid alpha-glucosidase (rhGAA) in treatment of infantile-onset Pompe disease.


METHODS
We enrolled 8 infant patients who had Pompe disease with GAA activity <1% of normal, cardiomyopathy, and hypotonia. In the 52-week initial phase, rhGAA was infused intravenously at 10 mg/kg weekly; an extension phase continued survivors' treatment with 10 to 20 mg/kg of rhGAA weekly or 20 mg/kg every 2 weeks for as long as 153 weeks. Safety measurements included adverse events, laboratory tests, and anti-rhGAA antibody titers. Efficacy evaluations included survival, ventilator use, echocardiograms, growth, and motor and cognitive function.


RESULTS
After 52 weeks of treatment, 6 of 8 patients were alive, and 5 patients were free of invasive ventilator support. Clinical improvements included ameliorated cardiomyopathy and improved growth and cognition. Five patients acquired new motor milestones; 3 patients walked independently. Four patients died after the initial study phase; the median age at death or treatment withdrawal for all patients was 21.7 months, significantly later than expected for patients who were not treated. Treatment was safe and well tolerated; no death was drug-related.


CONCLUSIONS
rhGAA improved ventilator-free survival, cardiomyopathy, growth, and motor function in patients with infantile-onset Pompe disease compared with outcomes expected for patients without treatment.
Kishnani
Priya Sunil
PS
Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA. kishn001@mc.duke.edu
Nicolino
Marc
M
Voit
Thomas
T
Rogers
R Curtis
RC
Tsai
Anne Chun-Hui
AC
Waterson
John
J
Herman
Gail E
GE
Amalfitano
Andreas
A
Thurberg
Beth L
BL
Richards
Susan
S
Davison
Mark
M
Corzo
Deyanira
D
Chen
Y T
YT
D001827:Body Height / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002312:Cardiomyopathy, Hypertrophic / Q000188:drug therapy / Q000209:etiology; D002657:Child Development; D005060:Europe / Q000453:epidemiology; D005260:Female; D006003:Glycogen / Q000378:metabolism; D006009:Glycogen Storage Disease Type II / Q000150:complications / Q000188:drug therapy* / Q000401:mortality*; D006311:Hearing Disorders / Q000209:etiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D008297:Male; D009123:Muscle Hypotonia / Q000188:drug therapy / Q000209:etiology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D012121:Respiration, Artificial; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D000520:alpha-Glucosidases / Q000378:metabolism / Q000627:therapeutic use*
D006003:Glycogen; C509951:GAA protein, human; D000520:alpha-Glucosidases