Table 4 Substrate reduction therapy: role in the variation of plasma lyso-Gb1 levels

Lukina et al. [44]

P, M

26 untreated GD1 patients, all with splenomegaly, thrombocytopenia, and/or anemia prior to treatment

Eliglustat 50 or 100 mg twice daily decreased plasma lyso-Gb1 levels from baseline to year 8 (624 ng/mL vs. 47.6 ng/mL), a percent reduction of 92%, with marked reductions at 1 year, which continued through 8 years of eliglustat therapy

Mistry et al. [45]

P, M

40 untreated GD patients

Despite elevated serum lyso-Gb1 levels in all patients at baseline (median value 61-fold above the ULN), median decreases in serum lyso-Gb1 levels of 59% and 84% were observed after 9 months (n = 37) and 4.5 years (n = 10) of eliglustat treatment, respectively

Peterschmit et al. [46]

P, M

62 untreated GD1 patients

The decrease in lyso-Gb1 levels correlated with improvements in baseline clinical parameters after eliglustat treatment (spleen, liver, hemoglobin, and platelets; all p < 0.05)

Murugesan et al. [39]

P, M

169 GD1 patients under treatment (155 on ERT and 14 on eliglustat)

Significantly lower levels of lyso-Gb1 were identified in patients treated with eliglustat than those receiving ERT (p < 0.001). Clinical indicators independently predictive of plasma lyso-Gb1 levels by multi-variate regression analysis were age (p < 0.001), serum chitotriosidase (p < 0.001), serum CCL18 (p = 0.001), splenectomy (p = 0.02), and treatment with eliglustat (p < 0.001). Interestingly, lyso-Gb1 levels were decreased to a greater extent among patients receiving eliglustat (9 patients) than those receiving ERT (47 patients) in comparable patient groups identified by propensity score matching

Smid et al., 2016 [74]

R

17 treatment-naïve or ERT experienced GD1 patients treated with

eliglustat (n = 6)

miglustat (n = 9)

ERT (n = 4)

Biochemical markers (chitotriosidase and lyso-Gb1) respond comparably in treatment-naïve patients receiving eliglustat treatment (n = 4) or ERT (n = 4), whereas the response was lower in miglustat-treated patients (n = 2). Specifically, in treatment-naïve patients, a median decrease in chitotriosidase levels of 89% [range 77–98], 88% [78–92], and 37% [29–46] were identified for eliglustat, ERT, and miglustat-treated patients respectively; for lyso-Gb1 levels this was 86% [78–93], 78% [65–91], and 48% [46–50], respectively

Kleytman et al. [75]

Real-world, longitudinal study

38 GD1 patients on long-term ERT for ≥ 2 years (mean 14.3 years; range 2 to 26 years) who had reached therapeutic goals before switching to eliglustat SRT (mean 3.1 years; range 5 months to 7 years)

Plasma lyso-Gb1 levels decreased significantly from 63.7 ng/ml (95% CI, 37.6–89.8) to 26.1 ng/ ml (95% CI, 15.7–36.6) (p < 0.0001) on eliglustat. In addition, 15 patients showed reductions of serum lyso-Gb1 to near normal levels (normal distribution of plasma lyso-Gb1 is 3.3 ng/ml)

Serum chitotriosidase levels also fell from 1,137 nmol/ml/h (95% CI, 145–2129) to 467 nmol/ml/h (95% CI, 209.9–724) (p = 0.002)