Summary of results after delivery of an AAV6-cF.IX vector via ATVRX in hemophilia B dogs naive or with previous exposure to an AAV-2 vector
| Group/ dog ID . | Age at time of injection . | Sex . | Weight, kg . | Serotype ATVRX administration . | NAB to AAV-2 capsid* . | Circulating cFIX,† ng/mL . | Bleeding episodes (expected‡) . | Follow-up, mo . |
|---|---|---|---|---|---|---|---|---|
| HB dogs previously exposed to AAV-2 | ||||||||
| E59 | 4.6 y | F | 21 | AAV-6 | 1:100 | 259 ± 50 | 1§ (21) | 46 |
| H27 | 2.4 y | F | 20 | AAA-6 | 1:1000 | 89 ± 47 | 0 (19) | 42 |
| D32 | 5.7 y | M | 18 | AAV-2 | 1:300 | < 10 | 8 (10) | 22 |
| B46 | 7.6 y | M | 24 | AAV-2 | 1:30 | < 10 | 4 (3) | 6 |
| Naive HB dogs | ||||||||
| M13 | 5 mo | F | 13 | AAV-6 | ND | 259 ± 37 | 0 (6) | 12 |
| M20 | 4 mo | M | 8 | AAV-6 | ND | 213 ± 25 | 0 (6) | 12 |
| Group/ dog ID . | Age at time of injection . | Sex . | Weight, kg . | Serotype ATVRX administration . | NAB to AAV-2 capsid* . | Circulating cFIX,† ng/mL . | Bleeding episodes (expected‡) . | Follow-up, mo . |
|---|---|---|---|---|---|---|---|---|
| HB dogs previously exposed to AAV-2 | ||||||||
| E59 | 4.6 y | F | 21 | AAV-6 | 1:100 | 259 ± 50 | 1§ (21) | 46 |
| H27 | 2.4 y | F | 20 | AAA-6 | 1:1000 | 89 ± 47 | 0 (19) | 42 |
| D32 | 5.7 y | M | 18 | AAV-2 | 1:300 | < 10 | 8 (10) | 22 |
| B46 | 7.6 y | M | 24 | AAV-2 | 1:30 | < 10 | 4 (3) | 6 |
| Naive HB dogs | ||||||||
| M13 | 5 mo | F | 13 | AAV-6 | ND | 259 ± 37 | 0 (6) | 12 |
| M20 | 4 mo | M | 8 | AAV-6 | ND | 213 ± 25 | 0 (6) | 12 |
There was no inhibitor to cF.IX in any of the dogs.
NAB indicates neutralizing antibody titer; and ND, not determined.
Measured at the time of vector readministration by ATVRX; values expressed as reciprocal dilutions.
Average ± SD of plateau levels > 3 months;
Based on an average of ∼ 5 bleeding episodes/year for untreated dogs.37
Two severe bleeding episodes and 3 postpartum bleeding episodes despite prophylactic plasma transfusion before readministration.