Table 2.
Hematological, visceral, and EKG interval values at baseline and post treatment with eliglustat.
| Patient | Current age (Years) | Age category (Years) | Sex | GBA genotype | Leucocyte acid β-glucosidase activity (nmol/h/mg) | CYPD26 status | Cardiac Comorbidities | Age category at diagnosis of GD (Years) | Duration of treatment (Years) | Eliglustat dosage |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 70 | >60 | F | p.Asn409Ser/84GG | NA | IM | Myocardial Infarction | <18 | 3 | 84 mg BiD |
| 2 | 56 | 40–60 | F | p.Asn409Ser/p.Asn409Ser | 0.2 | PM | Aortic Stenosis | 18–39 | 1 | 84 mg OD |
| 3 | 60 | 40–60 | F | p.Asn409Ser/p.Asn409Ser | 0.19 | IM | Myocardial Infarction | 18–39 | 13 | 84 mg BiD |
| 4 | 63 | >60 | M | p.Asn409Ser/p.Asn409Ser | NA | EM | Pericarditis | 40–60 | 4 | 84 mg OD* |
| 5 | 59 | 40–60 | M | p.Asn409Ser/p.Asn409Ser | NA | EM | Atrial Fibrillation | 40–60 | 9 | 84 mg BiD |
| 6 | 86 | >60 | M | p.Asn409Ser/p.Asn409Ser | NA | PM | Diastolic Dysfunction | 18–39 | 9 | 84 mg OD |
| 7 | 60 | 40–60 | F | p.Asn409Ser/p.Asn409Ser | NA | IM | Mildly ↑ QTc interval | 40–60 | 4 | 84 mg BiD |
| 8 | 74 | >60 | F | p.Asn409Ser/? | NA | PM | PVCs | >60 | 8 | 84 mg BiD |
| 9 | 14 | <18 | F | p.Asn409Ser/p.Asn409Ser | 0.3 | IM | WPW syndrome | <18 | 2 | 42 mg BiD** |
| 10 | 55 | >60 | F | p.Asn409Ser/L444P | NA | PM | PVCs | 18–39 | 12 | 84 mg OD |
| 11 | 63 | >60 | M | p.Asn409Ser/84GG | NA | EM | Aortic Stenosis | <18 | 9 | 84 mg BiD |
| 12 | 73 | >60 | M | p.Asn409Ser/p.Asn409Ser | NA | EM | Atrial Fibrillation | 18–39 | 9 | 84 mg OD*** |
| 13 | 68 | >60 | M | p.Asn409Ser/IVS2 + 1 | NA | PM | PAH/RBBB /LAFB | <18 | 1 | 84 mg OD |
| Patient | Hemoglobin (gm/dl) | Platelet (x1000/ul) | Liver volume | Spleen volume | GlcSph (ng/ml) | QTc interval (ms) | PR interval (ms) | QRS interval (ms) | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MN | MN | Baseline | Current | Baseline | Current | Baseline | Current | Baseline | Current | |||
| 1 | 9.5 | 365 | NA | Splenectomized | 41 | 8.4 | 395 | 394 | 172 | 148 | 78 | 82 |
| 2 | 13.1 | 110 | 1.01 | 6.59 | 28.3 | 21.2 | 417 | NA | 166 | NA | 86 | NA |
| 3 | 13.3 | 184 | 0.92 | 1.53 | NA | 5 | 406 | 414 | 141 | 155 | 90 | 88 |
| 4 | 15 | 140 | 0.71 | 2.25 | 83 | 14 | 428 | 348 | 164 | 164 | 102 | 108 |
| 5 | 15.1 | 188 | 0.77 | 2.04 | 9 | 5 | 430 | 416 | 178 | 186 | 94 | 84 |
| 6 | 15.2 | 197 | 0.89 | 3.36 | 99.3 | 2 | 481 | 524 | 176 | 212 | 150 | 168 |
| 7 | 13.1 | 251 | 0.59 | 0.88 | 9 | 1.6 | 422 | 425 | 142 | 159 | 87 | 82 |
| 8 | 12.5 | 279 | 0.76 | Splenectomized | NA | 15 | NA | NA | NA | NA | NA | NA |
| 9 | 13.4 | 256 | NA | 7.96 | 70 | 4 | 408 | NA | 80 | NA | 76 | NA |
| 10 | 14.3 | 104 | 1.12 | 3.8 | 7 | 1 | NA | 431 | NA | 172 | NA | 98 |
| 11 | 17.8 | 142 | 1.11 | 4.76 | 46.4 | 24.06 | 413 | 459 | 201 | 221 | 82 | 135 |
| 12 | 12.5 | 91 | 0.61 | 1.53 | 127.1 | 4 | 397 | 406 | 150 | 164 | 184 | 89 |
| 13 | 16 | 251 | 0.68 | Splenectomized | 39 | 18.5 | NA | 468 | NA | 228 | NA | 162 |
Table lists the actual values for hematological, visceral, disease biomarker and EKG intervals. The patients were divided into the following age categories: <18, 18–39, 40–60, >60 years. The difference in EKG intervals pre and post treatment was statistically and clinically insignificant. All patients showed expected response to eliglustat SRT with significant decline in GlcSph. GlcSph, Glucosylsphingosine; MN, Multiples of normal organ size; NA, Not available; PAH, Pulmonary arterial hypertension; WPW, Wolff Parkinson White syndrome; PVC, Premature ventricular contractions; PM, Poor metabolizer; IM, Intermediate metabolizer; EM, Extensive metabolizer; BID, twice daily; OD, Once daily. Leucocyte acid β-glucosidase activity normal range: 7.5–14.5 nmol/h/mg protein. Plasma glucosylsphingosine normal range: ≤1 ng/mL. *Dose reduced due to adverse effect of diarrhea. **Dose adjusted according to weight (<50 kg). ***Dose adjusted due to persistent atrial fibrillation and uncontrolled hypertension.