Table 1. Summary of recently reported AAV gene therapy trial results.
| Sponsor | Hemophilia | Vector | Manufacturing | Dose (vg/kg) | Liver
enzyme elevation † |
Effective
immuno- suppression? |
Transgene
expression (% normal) |
Ref. |
|---|---|---|---|---|---|---|---|---|
| SJCRH/UCL | HB | AAV8-FIX-WT | Plasmid DNA/
mammalian cell line |
2 × 10 11 – 2 × 10 12 | 4/6 | Yes | 2–5% | 98, 99 |
| Spark | HB | SPK100-FIX-
Padua |
Plasmid DNA/
mammalian cell line |
5 × 10 11 | 2/10 | Yes | ~30% | 100 |
| Shire | HB | AAV8-FIX-
Padua |
Plasmid DNA/
mammalian cell line |
2 × 10 11 – 3 × 10 12 | NR | No | 0–20% | 107, 108 |
| uniQure | HB | AAV5-FIX-WT | Baculovirus/
insect cell line |
5 × 10 12 – 2 × 10 13 | 2/5 | Yes | 3–12% | 102 |
| Biomarin | HA | AAV5-BDD-
FVIII |
Baculovirus/
insect cell line |
6 × 10 12 – 6 × 10 13 | 7/7 | Yes | 19–164% | 109 |
Abbreviations: AAV, adeno-associated virus; HA, hemophilia A; HB, hemophilia B; NR, not reported; Ref., reference; SJCRH/UCL, St Jude Children’s Research Hospital/University College of London; BDD, B-domain deleted.
†
(Number of subjects in highest-dose cohort who experienced increased alanine aminotransferase)/(number of subjects in highest-dose cohort)