Long-term effects of eliglustat on skeletal manifestations in clinical trials of patients with Gaucher disease type 1

Timothy M. Cox; Joel Charrow; Elena Lukina; Pramod K. Mistry; Meredith C. Foster; M. Judith Peterschmitt

doi:10.1016/j.gim.2022.10.011

Long-term effects of eliglustat on skeletal manifestations in clinical trials of patients with Gaucher disease type 1

Timothy M. Cox^*, Joel Charrow, Elena Lukina, Pramod K. Mistry, Meredith C. Foster, M. Judith Peterschmitt

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Purpose: Most patients with Gaucher disease have progressive and often disabling skeletal manifestations. We examined the long-term effect of eliglustat treatment on bone outcomes in clinical trials in adults with Gaucher disease type 1. Methods: Data from 4 completed phase 2 and 3 trials were evaluated in treatment-naïve patients or patients switching to eliglustat from enzyme replacement therapy (ERT). Results: Overall, 319 of 393 (81%) eliglustat-treated patients remained in their trials until completion or commercial eliglustat became available. Mean eliglustat treatment duration ranged from 3.3 to 6.5 years. In treatment-naïve patients and ERT-switch patients, frequency and severity of bone pain decreased during eliglustat treatment. Mean lumbar spine T-scores shifted from abnormal to normal in treatment-naïve patients and remained in the healthy reference range or improved modestly in ERT-switch patients. Mean total bone marrow burden score shifted from marked-to-severe to moderate in treatment-naïve patients and remained moderate in ERT-switch patients. MIP-1β (marker of active bone disease) was elevated at baseline and decreased to the healthy reference range in treatment-naïve patients and remained in the healthy reference range among ERT-switch patients. Conclusion: These findings confirm the long-term efficacy of eliglustat on skeletal complications of Gaucher disease in treatment-naïve and ERT-switch patients.

Original language	English (US)
Article number	100329
Journal	Genetics in Medicine
Volume	25
Issue number	2
DOIs	https://doi.org/10.1016/j.gim.2022.10.011
State	Published - Feb 2023

Funding

The eliglustat clinical trials were sponsored by Sanofi . The authors thank the participating patients, who were compensated for travel expenses, and health care professionals, whose institutions received funding for clinical trial-related expenses from Sanofi . We also thank Laurie LaRusso of Chestnut Communications for medical writing support funded by Sanofi , Lisa Underhill (Director of Scientific Communications and Publications for eliglustat, Sanofi Global Medical Affairs) for writing assistance and critical review of the manuscript, and Sebastiaan J.M. Gaemers (Sanofi, Global Pharmacovigilance) for critical review of the manuscript.

Keywords

Acid β-glucosidase deficiency
Eliglustat
Gaucher disease type 1
Skeletal manifestations
Substrate reduction therapy

ASJC Scopus subject areas

Genetics(clinical)

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10.1016/j.gim.2022.10.011

Cite this

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title = "Long-term effects of eliglustat on skeletal manifestations in clinical trials of patients with Gaucher disease type 1",

abstract = "Purpose: Most patients with Gaucher disease have progressive and often disabling skeletal manifestations. We examined the long-term effect of eliglustat treatment on bone outcomes in clinical trials in adults with Gaucher disease type 1. Methods: Data from 4 completed phase 2 and 3 trials were evaluated in treatment-na{\"i}ve patients or patients switching to eliglustat from enzyme replacement therapy (ERT). Results: Overall, 319 of 393 (81%) eliglustat-treated patients remained in their trials until completion or commercial eliglustat became available. Mean eliglustat treatment duration ranged from 3.3 to 6.5 years. In treatment-na{\"i}ve patients and ERT-switch patients, frequency and severity of bone pain decreased during eliglustat treatment. Mean lumbar spine T-scores shifted from abnormal to normal in treatment-na{\"i}ve patients and remained in the healthy reference range or improved modestly in ERT-switch patients. Mean total bone marrow burden score shifted from marked-to-severe to moderate in treatment-na{\"i}ve patients and remained moderate in ERT-switch patients. MIP-1β (marker of active bone disease) was elevated at baseline and decreased to the healthy reference range in treatment-na{\"i}ve patients and remained in the healthy reference range among ERT-switch patients. Conclusion: These findings confirm the long-term efficacy of eliglustat on skeletal complications of Gaucher disease in treatment-na{\"i}ve and ERT-switch patients.",

keywords = "Acid β-glucosidase deficiency, Eliglustat, Gaucher disease type 1, Skeletal manifestations, Substrate reduction therapy",

author = "Cox, {Timothy M.} and Joel Charrow and Elena Lukina and Mistry, {Pramod K.} and Foster, {Meredith C.} and Peterschmitt, {M. Judith}",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2023",

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doi = "10.1016/j.gim.2022.10.011",

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AU - Cox, Timothy M.

AU - Charrow, Joel

AU - Lukina, Elena

AU - Mistry, Pramod K.

AU - Foster, Meredith C.

AU - Peterschmitt, M. Judith

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N2 - Purpose: Most patients with Gaucher disease have progressive and often disabling skeletal manifestations. We examined the long-term effect of eliglustat treatment on bone outcomes in clinical trials in adults with Gaucher disease type 1. Methods: Data from 4 completed phase 2 and 3 trials were evaluated in treatment-naïve patients or patients switching to eliglustat from enzyme replacement therapy (ERT). Results: Overall, 319 of 393 (81%) eliglustat-treated patients remained in their trials until completion or commercial eliglustat became available. Mean eliglustat treatment duration ranged from 3.3 to 6.5 years. In treatment-naïve patients and ERT-switch patients, frequency and severity of bone pain decreased during eliglustat treatment. Mean lumbar spine T-scores shifted from abnormal to normal in treatment-naïve patients and remained in the healthy reference range or improved modestly in ERT-switch patients. Mean total bone marrow burden score shifted from marked-to-severe to moderate in treatment-naïve patients and remained moderate in ERT-switch patients. MIP-1β (marker of active bone disease) was elevated at baseline and decreased to the healthy reference range in treatment-naïve patients and remained in the healthy reference range among ERT-switch patients. Conclusion: These findings confirm the long-term efficacy of eliglustat on skeletal complications of Gaucher disease in treatment-naïve and ERT-switch patients.

AB - Purpose: Most patients with Gaucher disease have progressive and often disabling skeletal manifestations. We examined the long-term effect of eliglustat treatment on bone outcomes in clinical trials in adults with Gaucher disease type 1. Methods: Data from 4 completed phase 2 and 3 trials were evaluated in treatment-naïve patients or patients switching to eliglustat from enzyme replacement therapy (ERT). Results: Overall, 319 of 393 (81%) eliglustat-treated patients remained in their trials until completion or commercial eliglustat became available. Mean eliglustat treatment duration ranged from 3.3 to 6.5 years. In treatment-naïve patients and ERT-switch patients, frequency and severity of bone pain decreased during eliglustat treatment. Mean lumbar spine T-scores shifted from abnormal to normal in treatment-naïve patients and remained in the healthy reference range or improved modestly in ERT-switch patients. Mean total bone marrow burden score shifted from marked-to-severe to moderate in treatment-naïve patients and remained moderate in ERT-switch patients. MIP-1β (marker of active bone disease) was elevated at baseline and decreased to the healthy reference range in treatment-naïve patients and remained in the healthy reference range among ERT-switch patients. Conclusion: These findings confirm the long-term efficacy of eliglustat on skeletal complications of Gaucher disease in treatment-naïve and ERT-switch patients.

KW - Acid β-glucosidase deficiency

KW - Eliglustat

KW - Gaucher disease type 1

KW - Skeletal manifestations

KW - Substrate reduction therapy

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Long-term effects of eliglustat on skeletal manifestations in clinical trials of patients with Gaucher disease type 1

Abstract

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Keywords

ASJC Scopus subject areas

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