Factor IX Expression Within the Normal Range Prevents Spontaneous Bleeds Requiring Treatment Following FLT180a Gene Therapy in Patients With Severe Hemophilia B: Long-term Follow-up Study of the B-Amaze Program
Highlights From the 63rd ASH Annual Meeting

Factor IX Expression Within the Normal Range Prevents Spontaneous Bleeds Requiring Treatment Following FLT180a Gene Therapy in Patients With Severe Hemophilia B: Long-term Follow-up Study of the B-Amaze Program

Pratima Chowdary1,2, Susan Shapiro, MA, BM BCh, FRCP, FRCPath3,4, Mike Makris, MD5, Gillian Evans6, Sara Boyce7, Kate Talks8, Gerry Dolan, MBChB, FRCP, FRCPath9, Ulrike Reiss10*, Mark Phillips1,2, Anne Riddell1, Maria Rita Peralta1, Michelle Quaye2, Ted Tuddenham1*, Alison Long11, Julie Krop11, and Amit Nathwani, MD, PhD1,2

1Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital, London, United Kingdom
2University College London, London, United Kingdom
3Oxford University Hospitals, Oxford, United Kingdom
4Oxford University, Oxford, United Kingdom
5University of Sheffield, Sheffield, United Kingdom
6Kent and Canterbury Hospital, Canterbury, United Kingdom
7University Hospital Southampton, Southampton, United Kingdom
8Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, GBR
9Haemostasis and Thrombosis Centre, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
10St Jude Children’s Research Hospital, Memphis, TN
11Freeline, Stevenage, United Kingdom

Key Data Points

Adaptive Dosing Design for B-AMAZE

The study design for the B-AMAZE study included an adaptive format to facilitate identification of the optimal dose of the FLT180a AAV vector that would produce stable FIX levels of 50-150% of the normal range in patients with moderate to severe hemophilia B over a 26 week study period. The study design also included prophylactic immunosuppression with prednisolone to minimze transaminitis. Tacrolimus was added to the prophylactic regimen for the dose 4 cohort.

Dose-dependent FIX Response to Treatment

The FIX response in the 10 participants and 4 dose cohorts for B-AMAZE demonstrated a dose dependence. Median (range) duration of followup was 27.2 (19.1–42.4) months. Nine of ten participants did not receive FIX prophylaxis after treatment with FLT180a. One patient lost FIX expression following transaminitis. Of the 9 participants with sustained expression, 1 experienced a traumatic bleed requiring FIX infusion and there were no spontaneous bleeds requiring FIX infusions.

RELATED CONTENT

Interactive Webinars
Image

Please enable the javascript to submit this form

Supported by educational grants from Bayer, BioMarin, CSL Behring, Freeline Therapeutics Limited, Pfizer Inc., Spark Therapeutics, and uniQure, Inc.

Essential SSL