Blood: Results of clinical trials of BAX 335 gene therapy for type B haemophilia

Type B haemophilia is caused by insufficient coagulation factor IX (FIX) activity due to mutations in the F9 gene.
gene therapy has the potential to maintain therapeutic FIX levels in patients with haemophiliac type B by importing functional human F9 genes into liver cells.
report the results of a new study, "BAX 335 hemophilia gene therapy clinical trial results: potential impact of CpG sequences on gene expression", published recently in the journal Blood.
BAX 335 Expression Box Pattern Map This is a phase 1/2 open label dose incremental study that investigates the efficacy and safety of BAX 335 (AskBio009, AAV8.sc-TTR-FIXR338Lopt), a FIXua Pad gene therapy based on type 8 adenovirus (AAV8) for patients with type B haemophilia.
report focuses on an interim analysis of safety, pharmacodynamic variables, effects on FIX activity, and immune response over a 12-month period.
8 adult male subjects (age 20-69 years, FIX activity range: 0.5%-2.0%), received 1 dose with FIX activity, FIX Padua level, liver enzyme level and PBMC-mediated immune response Bax335 intravenously at different dose levels, with a total of 3 dose levels: 2.0×1011, 1.0×1012 or 3.0×1012 carrier genomes/kg.
three subjects (37.5 per cent) had four serious adverse events, all of which were not thought to be related to BAX335.
no serious adverse events resulting from death.
no clinical thrombosis, inhibitors, or other FIX Padua targeted immunity were reported.
of FIX peak activity was detected in 7 (7/8) subjects, and FIX peak activity was dose-dependent (32.0%-58.5%).
one subject maintained therapeutic FIX activity at about 20% for 4 consecutive years without bleeding or alternative treatment, and in the other subjects, FIX activity lasted no more than 5-11 weeks.
anti-AAV8 Nab reaction is different from previous studies, corticosteroid therapy does not stabilize the loss of FIX activity.
, the researchers speculate that the loss of GM expression may have been caused by stimuli from a natural immune response, including the introduction of CpG oligonucleotides into the Bax 335 coding sequence through cryptic optimization.