TY - JOUR
T1 - Impact of elosulfase alfa in patients with morquio A syndrome who have limited ambulation
T2 - An open-label, phase 2 study
AU - Harmatz, Paul R.
AU - Mengel, Eugen
AU - Geberhiwot, Tarekegn
AU - Muschol, Nicole
AU - Hendriksz, Christian J.
AU - Burton, Barbara K.
AU - Jameson, Elisabeth
AU - Berger, Kenneth I.
AU - Jester, Andrea
AU - Treadwell, Marsha
AU - Sisic, Zlatko
AU - Decker, Celeste
N1 - Funding Information:
We acknowledge the participation of study patients and their families and the expert assistance of all study site coordinators and personnel. The authors are also grateful to Ismar Healthcare NV, funded by BioMarin Pharmaceutical Inc., for support in the process of manuscript development. This publication was supported, in part (Dr. Harmatz), by the National Center for Advancing Translational Sciences, National Institutes of Health (NIH), through UCSF-CTSI grant number UL1 TR000004. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
PY - 2017/2/1
Y1 - 2017/2/1
N2 - Efficacy and safety of elosulfase alfa enzyme replacement therapy (ERT) were assessed in an open-label, phase 2, multi-national study in Morquio A patients aged ≥5 years unable to walk ≥30 meters in the 6-min walk test. Patients received elosulfase alfa 2.0 mg/kg/week intravenously for 48 weeks. Efficacy measures were functional dexterity, pinch/grip strength, mobility in a modified timed 25-foot walk, pain, quality of life, respiratory function, and urine keratan sulfate (KS). Safety/tolerability was also assessed. Fifteen patients received elosulfase alfa, three patients discontinued ERT due to adverse events (two were grade 3 drug-related adverse events, the other was not drug-related), and two patients missed >20% of planned infusions; 10 completed treatment through 48 weeks and received ≥80% of planned infusions (Modified Per Protocol [MPP] population). The study population had more advanced disease than that enrolled in other trials. From baseline to week 48, MPP data showed biochemical efficacy (urine KS decreased 52.4%). The remaining efficacy results were highly variable due to challenges in test execution because of severe skeletal and joint abnormalities, small sample sizes, and clinical heterogeneity among patients. Eight patients showed improvements in one or more outcome measures; several patients indicated improvements not captured by the study assessments (e.g., increased energy, functional ability). The nature of adverse events was similar to other elosulfase alfa studies. This study illustrates the considerable challenges in objectively measuring impact of ERT in very disabled Morquio A patients and highlights the need to examine results on an individual basis.
AB - Efficacy and safety of elosulfase alfa enzyme replacement therapy (ERT) were assessed in an open-label, phase 2, multi-national study in Morquio A patients aged ≥5 years unable to walk ≥30 meters in the 6-min walk test. Patients received elosulfase alfa 2.0 mg/kg/week intravenously for 48 weeks. Efficacy measures were functional dexterity, pinch/grip strength, mobility in a modified timed 25-foot walk, pain, quality of life, respiratory function, and urine keratan sulfate (KS). Safety/tolerability was also assessed. Fifteen patients received elosulfase alfa, three patients discontinued ERT due to adverse events (two were grade 3 drug-related adverse events, the other was not drug-related), and two patients missed >20% of planned infusions; 10 completed treatment through 48 weeks and received ≥80% of planned infusions (Modified Per Protocol [MPP] population). The study population had more advanced disease than that enrolled in other trials. From baseline to week 48, MPP data showed biochemical efficacy (urine KS decreased 52.4%). The remaining efficacy results were highly variable due to challenges in test execution because of severe skeletal and joint abnormalities, small sample sizes, and clinical heterogeneity among patients. Eight patients showed improvements in one or more outcome measures; several patients indicated improvements not captured by the study assessments (e.g., increased energy, functional ability). The nature of adverse events was similar to other elosulfase alfa studies. This study illustrates the considerable challenges in objectively measuring impact of ERT in very disabled Morquio A patients and highlights the need to examine results on an individual basis.
KW - GALNS protein, human [supplementary concept]
KW - enzyme replacement therapy
KW - mobility limitation
KW - mucopolysaccharidosis IV
KW - physical endurance
KW - safety
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U2 - 10.1002/ajmg.a.38014
DO - 10.1002/ajmg.a.38014
M3 - Article
C2 - 27774754
AN - SCOPUS:84995968200
VL - 173
SP - 375
EP - 383
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 2
ER -