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

Abstract

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. 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). 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. These findings confirm the long-term efficacy of eliglustat on skeletal complications of Gaucher disease in treatment-naïve and ERT-switch patients.