Freeline/University College, London

The dose-finding B-AMAZE trial aims to maintain factor IX activity within the range 50% – 150%. Results from 10 patients treated at four dose levels reported at the ISTH Virtual 2020 Congress showed [1]:

Mean factor IX activity levels were 25% – 130% at week 3 and 32% – 160% at week 26 in all 10 patients
week 52 mean factor IX activity in two patients was 31% and 38%
week 104 mean factor IX activity in one patient was 38%, the same as at week 52
No bleeding episode required treatment with a FIX concentrate
Four patients developed transient transaminitis that required steroids; subsequently, three patients received prophylactic steroids to prevent transaminitis
FIX activity >150% was individually assessed for risk of thrombosis, leading to one patient being treated with a direct-acting oral anticoagulant

hilia: the prospect of lifelong freedom from spontaneous bleeds and bleeding complications for individuals and their carers. However, gene therapy entails a long-term commitment from patients, and current technology does not remove the risk of transmitting haemophilia to their children. Early results from clinical trials are very promising for most people; however, they should be interpreted cautiously as they are based on relatively few participants and short-term outcomes. The cost of gene therapy will be high but, if early evidence of efficacy and safety is confirmed in the longer term, it is likely to be cost-saving over the lifetime of the patient compared with prophylaxis with a recombinant factor. How it will compare with emicizumab and extended half-life factors is not known.

References

Chowdary P, Shapiro S, Makris M, et al. A Novel Adeno Associated Virus (AAV) Gene Therapy (FLT180a) Achieves Normal FIX Activity Levels in Severe Hemophilia B (HB) Patients (B-AMAZE Study) [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). Accessed 30 September 2020.