Gene therapy trials for hemophilia
| Sponsor . | Vector . | Status . | Factor level achieved . | Bleeding outcome . |
|---|---|---|---|---|
| Gene therapy trials for hemophilia A | ||||
| BioMarin (NCT03370913)70,71 | AAV-5, valoctogogene roxaparvovec | Phase 3, 6 × 1013 vg | N = 132; median FVIII 23% (R 11-61) | 3 y: bleeding events decreased 84% |
| Spark Therapeutics, Pfizer (NCT03003533, NCT03432520)72 | AAV-3 SPK-8011 | Phase 1/2, 5 × 1011-2 × 1012 vg | N = 18; 15/18 had mean OS FVIII 11+/− 6.8% at 52 wk | 33.4 mo: bleeding events decreased 91.5% |
| Gene therapy trials for hemophilia B | ||||
| Spark Therapeutics, Pfizer (NCT02484092)34 | SPK-9001, AAV, hFIX, R338L (Padua) variant | Phase 1/2a | N = 10; mean FIX 33.7 +/− 18.5% at 49 wk | 49 wk: bleeding events decreased 96% |
| uniQure, CSL Behring (NCT03489291)35,73 | AAV5-hFIX, etranacogene dezaparvovec (EtranaDez) R338L (Padua) variant | Phase 3, AMT-061 HOPE-B, 2 × 1013 vg | N = 53; mean FIX 36.9% at 18 mo | 18 mo: bleeding events decreased 64% |
| Freeline, St. Jude's, University College London, and Royal Free Hospital (NCT03641703)74,75 | AAV8 FLT-180a verbrinacogene setparvovec R338L (Padua) variant | Phase 1/2, 3.84 × 1011- 1.28 × 1012 vg | N = 10; mean FIX 67.4% (R 9-260) at mean 26.6 mo | Mean 26.6 mo: bleeding events decreased 76% |
| Sponsor . | Vector . | Status . | Factor level achieved . | Bleeding outcome . |
|---|---|---|---|---|
| Gene therapy trials for hemophilia A | ||||
| BioMarin (NCT03370913)70,71 | AAV-5, valoctogogene roxaparvovec | Phase 3, 6 × 1013 vg | N = 132; median FVIII 23% (R 11-61) | 3 y: bleeding events decreased 84% |
| Spark Therapeutics, Pfizer (NCT03003533, NCT03432520)72 | AAV-3 SPK-8011 | Phase 1/2, 5 × 1011-2 × 1012 vg | N = 18; 15/18 had mean OS FVIII 11+/− 6.8% at 52 wk | 33.4 mo: bleeding events decreased 91.5% |
| Gene therapy trials for hemophilia B | ||||
| Spark Therapeutics, Pfizer (NCT02484092)34 | SPK-9001, AAV, hFIX, R338L (Padua) variant | Phase 1/2a | N = 10; mean FIX 33.7 +/− 18.5% at 49 wk | 49 wk: bleeding events decreased 96% |
| uniQure, CSL Behring (NCT03489291)35,73 | AAV5-hFIX, etranacogene dezaparvovec (EtranaDez) R338L (Padua) variant | Phase 3, AMT-061 HOPE-B, 2 × 1013 vg | N = 53; mean FIX 36.9% at 18 mo | 18 mo: bleeding events decreased 64% |
| Freeline, St. Jude's, University College London, and Royal Free Hospital (NCT03641703)74,75 | AAV8 FLT-180a verbrinacogene setparvovec R338L (Padua) variant | Phase 1/2, 3.84 × 1011- 1.28 × 1012 vg | N = 10; mean FIX 67.4% (R 9-260) at mean 26.6 mo | Mean 26.6 mo: bleeding events decreased 76% |
AAV, adeno-associated virus; hFIX, human factor IX; OS, one stage FVIII activity assay; R, range.