TY - JOUR
T1 - Clinical relevance of endpoints in clinical trials for acid sphingomyelinase deficiency enzyme replacement therapy
AU - Jones, Simon A.
AU - McGovern, Margaret
AU - Lidove, Olivier
AU - Giugliani, Roberto
AU - Mistry, Pramod K.
AU - Dionisi-Vici, Carlo
AU - Munoz-Rojas, Maria Veronica
AU - Nalysnyk, Lubomyra
AU - Schecter, Alison D.
AU - Wasserstein, Melissa
N1 - Funding Information:
This study was funded by Sanofi Genzyme. Manuscript writing and editing were provided by Patrice C. Ferriola, PhD of KZE PharmAssociates, LLC and funded by Sanofi Genzyme. Dr. Christiane Strauss, MD, Radiology department, Groupe Hospitalier Diaconesses Croix St Simon, Paris, France contributed the images for Fig. 1 . Louis Lavoie and Leigh Ann White from Evidera conducted the literature searches and review of the identified publications and were funded by Sanofi Genzyme.
Publisher Copyright:
© 2020 The Authors
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - Background: Acid sphingomyelinase deficiency (ASMD) also known as Niemann-Pick disease, is a rare lysosomal storage disorder with a diverse disease spectrum that includes slowly progressive, chronic visceral (type B) and neurovisceral forms (intermediate type A/B), in addition to infantile, rapidly progressive fatal neurovisceral disease (type A). Purpose and methods: We review the published evidence on the relevance of splenomegaly and reduced lung diffusion capacity to the clinical burden of chronic forms of ASMD. Targeted literature searches were conducted to identify relevant ASMD and non-ASMD studies for associations between diffusing capacity of the lungs for carbon monoxide (DLCO) and splenomegaly, with clinical parameters and outcome measures. Results: Respiratory disease and organomegaly are primary and independent contributors to mortality, disease burden, and morbidity for patients with chronic ASMD. The degree of splenomegaly correlates with short stature, atherogenic lipid profile, and degree of abnormality of hematologic parameters, and thus may be considered a surrogate marker for bleeding risk, abnormal lipid profiles and possibly, liver fibrosis. Progressive lung disease is a prevalent clinical feature of chronic ASMD, contributing to a decreased quality of life (QoL) and an increased disease burden. In addition, respiratory-related complications are a major cause of mortality in ASMD. Conclusions: The reviewed evidence from ASMD natural history and observational studies supports the use of lung function and spleen volume as clinically meaningful endpoints in ASMD trials that translate into important measures of disease burden for patients.
AB - Background: Acid sphingomyelinase deficiency (ASMD) also known as Niemann-Pick disease, is a rare lysosomal storage disorder with a diverse disease spectrum that includes slowly progressive, chronic visceral (type B) and neurovisceral forms (intermediate type A/B), in addition to infantile, rapidly progressive fatal neurovisceral disease (type A). Purpose and methods: We review the published evidence on the relevance of splenomegaly and reduced lung diffusion capacity to the clinical burden of chronic forms of ASMD. Targeted literature searches were conducted to identify relevant ASMD and non-ASMD studies for associations between diffusing capacity of the lungs for carbon monoxide (DLCO) and splenomegaly, with clinical parameters and outcome measures. Results: Respiratory disease and organomegaly are primary and independent contributors to mortality, disease burden, and morbidity for patients with chronic ASMD. The degree of splenomegaly correlates with short stature, atherogenic lipid profile, and degree of abnormality of hematologic parameters, and thus may be considered a surrogate marker for bleeding risk, abnormal lipid profiles and possibly, liver fibrosis. Progressive lung disease is a prevalent clinical feature of chronic ASMD, contributing to a decreased quality of life (QoL) and an increased disease burden. In addition, respiratory-related complications are a major cause of mortality in ASMD. Conclusions: The reviewed evidence from ASMD natural history and observational studies supports the use of lung function and spleen volume as clinically meaningful endpoints in ASMD trials that translate into important measures of disease burden for patients.
KW - Acid sphingomyelin deficiency
KW - Disease burden
KW - Lysosomal storage disorder
KW - Niemann-Pick Types A, B, /B
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U2 - 10.1016/j.ymgme.2020.06.008
DO - 10.1016/j.ymgme.2020.06.008
M3 - Review article
C2 - 32616389
AN - SCOPUS:85087213138
VL - 131
SP - 116
EP - 123
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
SN - 1096-7192
IS - 1-2
ER -