Table 2.
Key clinical trials and outcomes of AAV-mediated gene therapies in hemophilia.
| Study/trial name | Therapy | Target | Vector/serotype | Key findings | Adverse events | Clinical phase | Ref. |
|---|---|---|---|---|---|---|---|
| Initial FIX Study | AAV2-FIX | HB | AAV2 | Increased FIX to ~10%, then declined | Transient ALT elevation | Pilot study | (111) |
| UCL | AAV8-FIX | HB | AAV8 | Sustained FIX expression, improved transduction | Reduced immunoresistance (~25%) | Preclinical/early clinical | (112) |
| AMT-061/HOPE-B | Etranacogene | HB | AAV5 | Mean FIX activity 36.9%, ↓64% bleeding, ↓97% FIX use | No corticosteroids needed | Phase 3 | (113) |
| SPK-9001 | Fidanacogene | HB | Engineered AAV | FIX activity 22.9%, ABR ↓ from 8.9 to 0.4 | CpG-induced transaminitis | Phase 1/2 | (166) |
| BBM-H901 | Codon-optimized FIX | HB | Modified liver-tropic AAV | FIX ~36.9% at 1 yr. | ALT/aspartate elevation in 20% | Phase 1 | (115) |
| BMN 270 (BioMarin) | Codon-optimized FVIII | HA | AAV (B-domain) | Mean FVIII ↑ to 41.9 IU/dL | ALT increase | Phase 3 | (116) |
| SPK-8011 | Codon-optimized FVIII | HA | Bioengineered LK03 capsid | 16/18 maintained FVIII expression | ALT-related expression loss in 2 | Phase 3 | (117) |
“↑” Signifies an increase (for instance, in FVIII or FIX activity), whereas “↓” represents a decrease (such as in bleeding rate or factor consumption). The symbol “~” signifies approximately.