Table 1.
Baseline patient demographics and treatment phase outcomes.
| Parameter | Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 |
|---|---|---|---|---|---|
| Age (years) | 48 | 39 | 39 | 37 | 29 |
| GLA mutation | p.Gln321Arg | p.Ser345Pro | p.Ala143Pro | p.Ala143Pro | p.Tyr134Ser |
| Age at diagnosis (years) | 36 | 29 | 0 | 4 | 14 |
| Age started ET (years) | 36 | 33 | 36 | 26 | 29 |
| Fabry symptoms at baseline | |||||
| Acroparesthesia | x | ||||
| Angiokeratoma | x | x | x | x | |
| Cardiomyopathy | x | x | x | ||
| Chronic kidney disease | x | ||||
| Cold intolerance | x | ||||
| Corneal verticillata | x | x | x | ||
| Gastrointestinal | x | x | x | x | |
| Heat intolerance | x | ||||
| Hypertension | x | x | |||
| Hypohidrosis | x | x | x | ||
| Headaches and migraines | x | ||||
| Pain | x | x | |||
| Peripheral sensory neuropathy | x | ||||
| Proteinuria | x | x | |||
| Tinnitus or hearing loss | x | x | x | ||
| Mobilization agents | G-CSF | G-CSF + plerixafor | G-CSF + plerixafor | G-CSF + plerixafor | G-CSF |
| Apheresis yield CD34+ cells ×106/kg | 8.4 | 9.2 | 18.1 | 9.0 | 5.1 |
| Drug product VCN (copies/genome) | 0.68 | 1.43 | 0.81 | 1.37 | 1.13 |
| Drug product infused: CD34+ cells ×106/kg | 4.9 | 6.4 | 13.8 | 6.2 | 3.1 |
| Colony PCRa | |||||
| Mock | 0% | 0% | 0% | ND | ND |
| LV-AGA (Drug Product) | 52% | 62% | 54% | ND | ND |
| Colony PCR on Day −2 BM samples | ND | 0/86 (0%) | 0/88 (0%) | 0/92 (0%) | 0/88 (0%) |
| Colony PCR on Day 28 BM samples | 10/28 (35.7%) | 70/92 (76.1%) | 63/90 (70.0%) | 52/92 (56.5%) | 56/88 (63.6%) |
| Actual study day for colony PCR | Day 33 | Day 28 | Day 28 | Day 28 | Day 32 |
| Day −2 BM α-gal A nmoles/hr/mg | 0.3 | 1.0 | 1.6 | 1.0 | 0.8 |
| Day 28 BM α-gal A nmoles/hr/mg | 220 | 350 | 169 | 320 | 569 |
| Time to engraftment (absolute neutrophil count >0.5 x 109 cells per L)b | Day 12 | Day 13 | Day 11 | Day 11 | Day 12 |
| Time to engraftment (platelet count >20 x 109 per L) | Day 12 | Day 12 | Day 12 | Day 11 | Day 12 |
| Day −2 BM VCN copies/genome | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
| Day 28 BM VCNc copies/genome | 0.47 | 0.89 | 0.33 | 1.10 | 1.21 |
| Maximum PB VCN copies/genome | 0.55 | 1.10 | 0.78 | 0.65 | 1.30 |
| First Day Plasma α-Gal A activity observed | Day 8d | Day 7 | Day 6 | Day 6 | Day 7 |
| Days from Cell Infusion to ET withdrawal | +548 | ND | −41e | +214 | ND |
BM bone marrow, ET enzyme therapy, ND not done, PB peripheral blood, PCR polymerase chain reaction, VCN vector copy number.
aTransduction efficiency—colony PCR assays.
bRef. 35.
cDay 28–33.
dDefined by activity >2 times the average of pretransplant values.
ePatient 3 discontinued ET prior to infusion and chose not to resume.