Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study.
OBJECTIVE
The objective of this Phase 3 study was to confirm the efficacy and safety of recombinant human arylsulfatase B (rhASB) treatment of mucopolysaccharidosis type VI (MPS VI; Maroteaux-Lamy syndrome), a rare, fatal lysosomal storage disease with no effective treatment.


METHODS
Thirty-nine patients with MPS VI were evaluated in a randomized, double-blind, placebo-controlled, multicenter, multinational study for 24 weeks. The primary efficacy variable was the distance walked in a 12-minute walk test (12MWT), whereas the secondary efficacy variables were the number of stairs climbed in a 3-minute stair climb (3MSC) and the level of urinary glycosaminoglycan (GAG) excretion. All patients received drug in an open-label extension period for an additional 24 weeks.


RESULTS
After 24 weeks, patients receiving rhASB walked on average 92 meters (m) more in the 12MWT (p=.025) and 5.7 stairs per minute more 3MSC (p=.053) than patients receiving placebo. Continued improvement was observed during the extension study. Urinary GAG declined by -227+/-18 microg/mg more with rhASB than placebo (p<.001). Infusions were generally safe and well tolerated. Patients exposed to drug experienced positive clinical benefit despite the presence of antibody to the protein.


CONCLUSIONS
rhASB significantly improves endurance, reduces GAG, and has an acceptable safety profile.
Harmatz
Paul
P
Children's Hospital & Research Center at Oakland, California 94609, USA, and Children's Hospital, University of Mainz, Germany. Pharmatz@mail.cho.org
Giugliani
Roberto
R
Schwartz
Ida
I
Guffon
Nathalie
N
Teles
Elisa Leão
EL
Miranda
M Clara Sá
MC
Wraith
J Edmond
JE
Beck
Michael
M
Arash
Laila
L
Scarpa
Maurizio
M
Yu
Zi-Fan
ZF
Wittes
Janet
J
Berger
Kenneth I
KI
Newman
Mary S
MS
Lowe
Ann M
AM
Kakkis
Emil
E
Swiedler
Stuart J
SJ
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D002648:Child; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D006025:Glycosaminoglycans / Q000652:urine; D006801:Humans; D016014:Linear Models; D008297:Male; D009087:Mucopolysaccharidosis VI / Q000188:drug therapy*; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012449:Safety; D016138:Walking
D006025:Glycosaminoglycans; D011994:Recombinant Proteins; D020051:N-Acetylgalactosamine-4-Sulfatase