A randomized study of alglucosidase alfa in late-onset Pompe's disease.
BACKGROUND
Pompe's disease is a metabolic myopathy caused by a deficiency of acid alpha glucosidase (GAA), an enzyme that degrades lysosomal glycogen. Late-onset Pompe's disease is characterized by progressive muscle weakness and loss of respiratory function, leading to early death. We conducted a randomized, placebo-controlled trial of alglucosidase alfa, a recombinant human GAA, for the treatment of late-onset Pompe's disease.


METHODS
Ninety patients who were 8 years of age or older, ambulatory, and free of invasive ventilation were randomly assigned to receive biweekly intravenous alglucosidase alfa (20 mg per kilogram of body weight) or placebo for 78 weeks at eight centers in the United States and Europe. The two primary end points were distance walked during a 6-minute walk test and percentage of predicted forced vital capacity (FVC).


RESULTS
At 78 weeks, the estimated mean changes from baseline in the primary end points favored alglucosidase alfa (an increase of 28.1+/-13.1 m on the 6-minute walk test and an absolute increase of 3.4+/-1.2 percentage points in FVC; P=0.03 and P=0.006, respectively). Similar proportions of patients in the two groups had adverse events, serious adverse events, and infusion-associated reactions; events that occurred only in patients who received the active study drug included anaphylactic reactions and infusion-associated reactions of urticaria, flushing, hyperhidrosis, chest discomfort, vomiting, and increased blood pressure (each of which occurred in 5 to 8% of the patients).


CONCLUSIONS
In this study population, treatment with alglucosidase alfa was associated with improved walking distance and stabilization of pulmonary function over an 18-month period. (ClinicalTrials.gov number, NCT00158600.)
van der Ploeg
Ans T
AT
Department of Pediatrics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands. a.vanderploeg@erasmusmc.nl
Clemens
Paula R
PR
Corzo
Deyanira
D
Escolar
Diana M
DM
Florence
Julaine
J
Groeneveld
Geert Jan
GJ
Herson
Serge
S
Kishnani
Priya S
PS
Laforet
Pascal
P
Lake
Stephen L
SL
Lange
Dale J
DJ
Leshner
Robert T
RT
Mayhew
Jill E
JE
Morgan
Claire
C
Nozaki
Kenkichi
K
Park
Dorothy J
DJ
Pestronk
Alan
A
Rosenbloom
Barry
B
Skrinar
Alison
A
van Capelle
Carine I
CI
van der Beek
Nadine A
NA
Wasserstein
Melissa
M
Zivkovic
Sasa A
SA
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000704:Analysis of Variance; D002648:Child; D004342:Drug Hypersensitivity / Q000209:etiology; D005260:Female; D006009:Glycogen Storage Disease Type II / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D014797:Vital Capacity / Q000187:drug effects; D016138:Walking; D055815:Young Adult; D000520:alpha-Glucosidases / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*
D007074:Immunoglobulin G; C509951:GAA protein, human; D000520:alpha-Glucosidases