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

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.
Competing Interests: Conflict of Interest T.M.C. was a principal investigator on the Sanofi-sponsored eliglustat ENCORE trial and has received honoraria, travel reimbursement, and grant/research support from Takeda, Shire Pharmaceuticals and Sanofi. J.C. was a principal investigator on the Sanofi-sponsored eliglustat EDGE trial; has received honoraria for consultation and advisory board participation from Sanofi, Synageva, Shire, BioMarin, National Gaucher Foundation, and Pfizer/Protalix; and has received lecture fees or honoraria for speaking at the invitation of Sanofi and SIMD North American Metabolic Academy. E.L. was a principal investigator on the Sanofi-sponsored eliglustat phase 2, ENGAGE, ENCORE, and EDGE trials and has received honoraria and travel reimbursement and participates on advisory boards of Sanofi and Shire. P.K.M. was a principal investigator on the Sanofi-sponsored eliglustat ENGAGE trial, is a member of the International Collaborative Gaucher Group (ICGG) Gaucher Registry North American Advisory Board, and has received research support, honoraria, and travel reimbursement from Sanofi. M.J.P. and M.C.F. are employees of Sanofi and own shares and/or stock options in the company.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)