Two years of efficacy of oral eliglustat in treatment-naïve and switch patients enrolled in the International Collaborative Gaucher Group Gaucher registry

Abstract

Eliglustat (Cerdelga, Sanofi Genzyme) is a first-line oral substrate reduction therapy for adults with Gaucher disease type 1 (GD1) with extensive, intermediate, or poor CYP2D6-metabolizer phenotypes (>90% of patients). Clinical trials have demonstrated long-term clinical improvement in all major disease manifestations in treatment-naive patients and long-term stability in patients switching from enzyme-replacement therapy (ERT). We report real-world data from treatment-naive and ERT-switch patients enrolled in the International Collaborative Gaucher Group Gaucher (ICGG) Registry (NCT00358943/Sanofi Genzyme) who were treated with eliglustat for ≥1 year. Of 400 eliglustat-treated patients in the Registry as of July 2018, 238 had baseline and 2-year data (±1 year) for ≥1 key disease parameter: 15 treatment-naive (0 splenectomized) and 223 switch (43 splenectomized). Overall, 213 were from the United States, the first country to approve eliglustat. In treatment-naive patients, mean hemoglobin improved from 12.5 to 13.8 g/dL (p=0.004 n=14) mean platelet count improved from 113 to 158 x109/L (p=0.0002 n=13) mean spleen volume decreased from 9.4 to 4.2 multiples of normal (MN) (p=0.01, n=5), and mean liver volume was unchanged: 1.2 vs 1.1 MN (non-significant, n=5). In non‑splenectomized-switch patients, mean hemoglobin remained normal: 14.3 vs 14.1 g/dL (p=0.01, n=169) mean platelet count remained normal: 181 vs 184 x109/L (non-significant, n=169) mean spleen volume decreased from 2.9 to 2.5 MN (p=0.002, n=63), and mean liver volume remained stable at 0.9 MN (non-significant, n=63). In splenectomized-switch patients, mean hemoglobin remained stable: 13.5 to 13.4 g/dL (non-significant, n=36) mean platelet count increased from 295 to 319 x109/L (p=0.05, n=34) mean liver volume remained stable: 0.9 to 1 MN (non-significant, n=15). Mean chitotriosidase levels decreased in all groups, with significant reductions in treatment-naive patients (1325 to 308 nmol/mL/hr, p=0.03, n=6) and non-splenectomized-switch patients (838 to 725 nmol/mL/hr p=0.02, n=86). These real-world results are consistent with those reported in eliglustat clinical trials.