Follow-up on a Novel Adeno-Associated Virus (AAV) Gene Therapy (FLT180a) Achieving Normal FIX Activity Levels in Severe Hemophilia B (HB) Patients  (B-AMAZE Study)
Highlights From the 14th Annual Congress of EAHAD

Follow-up on a Novel Adeno-Associated Virus (AAV) Gene Therapy (FLT180a) Achieving Normal FIX Activity Levels in Severe Hemophilia B (HB) Patients
(B-AMAZE Study)

Pratima Chowdary,1,2 Susan Shapiro,3 Mike Makris,4 Gillian Evans,5 Sara Boyce,6 Kate Talks,7 Gerry Dolan,8 Ulrike Reiss,9 Mark Phillips,1,2 Anne Riddell,1 Maria Rita Peralta,1 Michelle Quaye,2 Ted Tuddenham,1 Andrew Smith,10 Alison Long,10 Julie Krop,10 Amit Nathwani1,2

1Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital, London, UK

2University College London, London, UK

3Oxford Haemophilia Centre, Oxford, UK

4University of Sheffield, Sheffield, UK

5Kent and Canterbury Hospital, Canterbury, UK

6University Hospital Southampton, Southampton, UK

7Newcastle Haemophilia Comprehensive Care Centre, Newcastle, UK

8St Thomas’ and Guy’s Hospital, London, UK

9St Jude Children’s Research, Memphis, TN, USA

10Freeline, Stevenage, UK

Key Data Points

Study Design

aPreviously reported as 4.5e11vg/kg; bPreviously reported as 1.5e12vg/kg;
cPreviously reported as 7.5e11vg/kg; dPreviously reported as 9.75e11vg/kg 

To assess the safety and efficacy of FLT180a, an adaptive dosing regimen was utilized, starting with 2 patients at the lowest dose of 3.8 x 1011 vg/kg and adjusting subsequent doses to optimize FIX expression while minimizing risk of thrombosis. The dose for the last cohort, Cohort 4, was 8.32 x 1011 vg/kg. Immune suppression procedures evolved during the trial, resulting in a prophylactic immune suppression regimen that included tacrolimus in Cohort 4.

FIX Activity

FIX activity based on the one-stage assay for the 4 subjects in Cohort 4 over the first 6 months following treatment with the AAVS3 vector and FIX-Padua transgene. Peak FIX activity was 150-250% and occurred between 50 and 140 days post-infusion. In 3 of 4 subjects, FIX levels have remained above 100%.

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