Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase).
OBJECTIVE
To confirm the efficacy and safety of recombinant human alpha-L-iduronidase (laronidase) in patients with mucopolysaccharidosis I (MPS I).


METHODS
This was a randomized, double-blinded, multinational study of 45 patients with MPS I administered 100 U/kg (0.58 mg/kg) laronidase, or placebo intravenously weekly for 26 weeks. The coprimary efficacy end points compared the median change from baseline to week 26 between groups in percentage of predicted normal forced vital capacity (FVC) and in 6-minute walk test (6MWT) distance through the use of the Wilcoxon rank sum test.


RESULTS
The laronidase (n=22) and placebo (n=23) groups had similar baseline characteristics. After 26 weeks, patients receiving laronidase compared with placebo showed mean improvements of 5.6 percentage points in percent of predicted normal FVC (median, 3.0; P=.009) and 38.1 meters in 6MWT distance (median, 38.5; P=.066; P=.039, analysis of covariance). Laronidase also significantly reduced hepatomegaly and urinary glycosaminoglycans, and, in more severely affected patients, improved sleep apnea/hypopnea and shoulder flexion. Laronidase was well-tolerated. Nearly all patients receiving enzyme had development of IgG antibodies, without apparent clinical effects.


CONCLUSIONS
In patients with MPS I, laronidase significantly improves respiratory function and physical capacity, reduces glycosaminoglycan storage, and has a favorable safety profile.
Wraith
James E
JE
Willink Biochemical Genetics Unit, Royal Manchester Children's Hospital, Manchester, United Kingdom. ed.wraith@cmmc.nhs.uk
Clarke
Lorne A
LA
Beck
Michael
M
Kolodny
Edwin H
EH
Pastores
Gregory M
GM
Muenzer
Joseph
J
Rapoport
David M
DM
Berger
Kenneth I
KI
Swiedler
Stuart J
SJ
Kakkis
Emil D
ED
Braakman
Tanja
T
Chadbourne
Elenie
E
Walton-Bowen
Karen
K
Cox
Gerald F
GF
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007068:Iduronidase / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008059:Mucopolysaccharidosis I / Q000150:complications / Q000188:drug therapy*; D011994:Recombinant Proteins; D012131:Respiratory Insufficiency / Q000188:drug therapy / Q000209:etiology; D018709:Statistics, Nonparametric
D011994:Recombinant Proteins; D007068:Iduronidase