Data of reported results of intravenously administered AAV-based gene therapy phase 1 to 3 trials for hemophilia A and B
| Sponsor . | Generic/product name . | NC no. . | Phase . | N . | Dose of vector (/kg BW) . | Expression level short term (1-6 mo)* . | 1 y (IU/dL or %) . | >2 y (IU/dL or %) . | Duration and stability . | Reference . |
|---|---|---|---|---|---|---|---|---|---|---|
| Hemophilia A | ||||||||||
| Biomarin Pharmaceuticals | Valoctocogene roxaparvovec (AAV5 BMN 270) | NCT02576795 | 1/2 | 7 | 6 × 1013 | Gradual increase up to 24 wk | 60 (median) 64 (mean) CSA | 36 (median) 26 (mean) | Expression declining after 1 y to 33 (mean) and 20 (median) after 3 y | 10,22 |
| BioMarin Pharmaceutical | Valoctocogene roxaparvovec (AAV5 BMN 270) | NCT03370913 | 3 | 134 | 6 × 1013 | n.a. | 23.9 (median) 42.9 (SD 45.5) CSA | n.a. | No long-term data available | 24 |
| Spark Therapeutics | SPK-8011, AAV LK03-co-BDD-F8 | NCT03003533 | 1/2 | 7 | 2 × 1012 | 16-49 (n = 5), response < 5 in 2 patients | n.a | 5.2-19.8 (n = 5) | Two patients lost expression | 25,26 |
| Sangamo Therapeutics/ Pfizer | Giroctocogene fitelparvovec SB-525, AAV6-co-BDD-F8 (ALTA-Study) | NCT03061201 | 1/2 | 5 | 3 × 1013 | Increase to normal range within 5 wk | 50.2 (median steady state) 80.1 mean (SD 93.3) | n.a. | 28,29 | |
| Bayer | BAY2599023 (DTX 201) AAVhu37- GET-8 study | NCT03588299 | 1/2 | 2 | 2 × 1013 | 12 and 72 | n.a | n.a | Follow-up too short for evaluation of durability | 27 |
| Hemophilia B | ||||||||||
| UCL/St JudesCRH | AAV8 FIX-WT | NCT00979238 | 1 | 6 | 2 × 1012 | 1.4-7.2 (range) (OSA) | 5.1 mean (SD 1.7) | Stable expression over 8 y | 9,20 | |
| Ultragenics Pharm | DTX101, AAVrh10FIX | NCT02618915 | 1/2 | 3 | 5 × 1012 | 12-20 (range) reached within 3-8 wk | Gradual decrease to baseline | Transient, short-term expression | 56 | |
| Baxalta/Takeda | AAV8-coF9-Padua Bax 335 | NCT01687608 | 1/2 | 2 | 3 × 1012 | 45.3 (mean peak levels) (range 32-59) (OSA) | n.a. | 20 (one patient) | Transient, short-term expression in 7; loss of expression in 6 out of 7 | 54,55 |
| UniQure BioPharma | AAV5-hFIX (AMT-060) | NCT02396342 | 1/2 | 5 | 2 × 1013 | 6.9 (mean) (95% CI, 2.6-11.3) (OSA) | n.a. | 7.4 (95% CI 4.2-10.6) | Stable expression over 5 y | 12,30 |
| Spark Therapeutics/ Pfizer | Fidanacogene elaparvovec SPK-9001, mutant AAV8-coF9-Padua Factor IX-long study | NCT03307980 | 1/2 | 10 | 5 × 1011 | 33.7 mean (SD 18.5) Range 14-81 (OSA) | n.a. | n.a. | 11 | |
| UniQure Biopharma | Etranacogene dezaparvovec AAV5-hFIXco-Padua (AMT-061) | NCT03489291 | 2b | 3 | 2 × 1013 | 47 (mean) (range 33.2-57.0) (OSA) | n.a. | n.a. | No long-term data available | 31 |
| Freeline Therapeutics | FLT180a (B-AMAZE) | NCT03369444 | 1 | 2 | 1.5 × 1012 | 160 (67-253) Mean (range at 26 wk) | n.a | n.a. | Studies continued with lower dose | 33 |
| UniQure Biopharma | AAV5-hFIXco-Padua (AMT-061)HOPE-B | NCT03569891 | 3 | 54 | 2 × 1013 | 37.2 (mean) 19.6 SD Range 1-97 (OSA) | n.a. | n.a | No long-term data available | 32 |
| Sponsor . | Generic/product name . | NC no. . | Phase . | N . | Dose of vector (/kg BW) . | Expression level short term (1-6 mo)* . | 1 y (IU/dL or %) . | >2 y (IU/dL or %) . | Duration and stability . | Reference . |
|---|---|---|---|---|---|---|---|---|---|---|
| Hemophilia A | ||||||||||
| Biomarin Pharmaceuticals | Valoctocogene roxaparvovec (AAV5 BMN 270) | NCT02576795 | 1/2 | 7 | 6 × 1013 | Gradual increase up to 24 wk | 60 (median) 64 (mean) CSA | 36 (median) 26 (mean) | Expression declining after 1 y to 33 (mean) and 20 (median) after 3 y | 10,22 |
| BioMarin Pharmaceutical | Valoctocogene roxaparvovec (AAV5 BMN 270) | NCT03370913 | 3 | 134 | 6 × 1013 | n.a. | 23.9 (median) 42.9 (SD 45.5) CSA | n.a. | No long-term data available | 24 |
| Spark Therapeutics | SPK-8011, AAV LK03-co-BDD-F8 | NCT03003533 | 1/2 | 7 | 2 × 1012 | 16-49 (n = 5), response < 5 in 2 patients | n.a | 5.2-19.8 (n = 5) | Two patients lost expression | 25,26 |
| Sangamo Therapeutics/ Pfizer | Giroctocogene fitelparvovec SB-525, AAV6-co-BDD-F8 (ALTA-Study) | NCT03061201 | 1/2 | 5 | 3 × 1013 | Increase to normal range within 5 wk | 50.2 (median steady state) 80.1 mean (SD 93.3) | n.a. | 28,29 | |
| Bayer | BAY2599023 (DTX 201) AAVhu37- GET-8 study | NCT03588299 | 1/2 | 2 | 2 × 1013 | 12 and 72 | n.a | n.a | Follow-up too short for evaluation of durability | 27 |
| Hemophilia B | ||||||||||
| UCL/St JudesCRH | AAV8 FIX-WT | NCT00979238 | 1 | 6 | 2 × 1012 | 1.4-7.2 (range) (OSA) | 5.1 mean (SD 1.7) | Stable expression over 8 y | 9,20 | |
| Ultragenics Pharm | DTX101, AAVrh10FIX | NCT02618915 | 1/2 | 3 | 5 × 1012 | 12-20 (range) reached within 3-8 wk | Gradual decrease to baseline | Transient, short-term expression | 56 | |
| Baxalta/Takeda | AAV8-coF9-Padua Bax 335 | NCT01687608 | 1/2 | 2 | 3 × 1012 | 45.3 (mean peak levels) (range 32-59) (OSA) | n.a. | 20 (one patient) | Transient, short-term expression in 7; loss of expression in 6 out of 7 | 54,55 |
| UniQure BioPharma | AAV5-hFIX (AMT-060) | NCT02396342 | 1/2 | 5 | 2 × 1013 | 6.9 (mean) (95% CI, 2.6-11.3) (OSA) | n.a. | 7.4 (95% CI 4.2-10.6) | Stable expression over 5 y | 12,30 |
| Spark Therapeutics/ Pfizer | Fidanacogene elaparvovec SPK-9001, mutant AAV8-coF9-Padua Factor IX-long study | NCT03307980 | 1/2 | 10 | 5 × 1011 | 33.7 mean (SD 18.5) Range 14-81 (OSA) | n.a. | n.a. | 11 | |
| UniQure Biopharma | Etranacogene dezaparvovec AAV5-hFIXco-Padua (AMT-061) | NCT03489291 | 2b | 3 | 2 × 1013 | 47 (mean) (range 33.2-57.0) (OSA) | n.a. | n.a. | No long-term data available | 31 |
| Freeline Therapeutics | FLT180a (B-AMAZE) | NCT03369444 | 1 | 2 | 1.5 × 1012 | 160 (67-253) Mean (range at 26 wk) | n.a | n.a. | Studies continued with lower dose | 33 |
| UniQure Biopharma | AAV5-hFIXco-Padua (AMT-061)HOPE-B | NCT03569891 | 3 | 54 | 2 × 1013 | 37.2 (mean) 19.6 SD Range 1-97 (OSA) | n.a. | n.a | No long-term data available | 32 |
Only data for the highest dose of vector administered in the phase 1/2 studies are given. N = number of patients included. n.a., not available.
FVIII or FIX activity levels were obtained by OSAs or CSAs. In case no assay type is specified in the table, this is unknown.