A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome).
OBJECTIVE
To evaluate the safety and efficacy of recombinant human iduronate-2-sulfatase (idursulfase) in the treatment of mucopolysaccharidosis II.


METHODS
Ninety-six mucopolysaccharidosis II patients between 5 and 31 years of age were enrolled in a double-blind, placebo-controlled trial. Patients were randomized to placebo infusions, weekly idursulfase (0.5 mg/kg) infusions or every-other-week infusions of idursulfase (0.5 mg/kg). Efficacy was evaluated using a composite endpoint consisting of distance walked in 6 minutes and the percentage of predicted forced vital capacity based on the sum of the ranks of change from baseline.


RESULTS
Patients in the weekly and every-other-week idursulfase groups exhibited significant improvement in the composite endpoint compared to placebo (P = 0.0049 for weekly and P = 0.0416 for every-other-week) after one year. The weekly dosing group experienced a 37-m increase in the 6-minute-walk distance (P = 0.013), a 2.7% increase in percentage of predicted forced vital capacity (P = 0.065), and a 160 mL increase in absolute forced vital capacity (P = 0.001) compared to placebo group at 53 weeks. Idursulfase was generally well tolerated, but infusion reactions did occur. Idursulfase antibodies were detected in 46.9% of patients during the study.


CONCLUSIONS
This study supports the use of weekly infusions of idursulfase in the treatment of mucopolysaccharidosis II.
Muenzer
Joseph
J
University of North Carolina, Department of Pediatrics, Chapel Hill, NC 27599, USA.
Wraith
James E
JE
Beck
Michael
M
Giugliani
Roberto
R
Harmatz
Paul
P
Eng
Christine M
CM
Vellodi
Ashok
A
Martin
Rick
R
Ramaswami
Uma
U
Gucsavas-Calikoglu
Muge
M
Vijayaraghavan
Suresh
S
Wendt
Susanne
S
Wendt
Suzanne
S
Puga
Ana Cristina
AC
Puga
Antonio
A
Ulbrich
Brian
B
Shinawi
Marwan
M
Cleary
Maureen
M
Piper
Diane
D
Conway
Anne Marie
AM
Conway
Ann Marie
AM
Kimura
Alan
A
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004361:Drug Tolerance; D006023:Glycoproteins / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007066:Iduronate Sulfatase / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D016532:Mucopolysaccharidosis II / Q000188:drug therapy* / Q000503:physiopathology; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012449:Safety; D014797:Vital Capacity / Q000187:drug effects
D006023:Glycoproteins; C018322:IDS protein, human; D011994:Recombinant Proteins; D007066:Iduronate Sulfatase