Freeline presents data on AAV-based gene therapies for Haemophilia B at EAHAD
London, 7 February 2020 – Freeline, a biotechnology company focused on developing curative gene therapies for chronic systemic diseases, today presented further data from its Phase 1/2 B-AMAZE trial investigating a novel gene therapy, FLT180a, for Haemophilia B at the 13th Annual Congress of the European Association for Haemophilia and Allied Disorder (EAHAD), The Hague, Netherlands.
The study, which has an adaptive design, has dosed 2 patients in 4 separate dose cohorts. The data presented today suggests that the fourth dose cohort at 9.75e11 vg/kg has the potential to provide durable Factor IX (FIX) activity in the normal range.
“These data confirm the progress we are making towards achieving Factor IX levels in the normal range for patients with severe or moderately severe Haemophilia B,” said Professor Amit Nathwani, Founder and Chief Scientific Officer of Freeline and Professor at UCL Cancer Institute. “The progress also demonstrates the efficiency of our next generation AAV capsid and highlights the significant opportunity we have to offer gene therapies for Haemophilia A and other monogenic disorders.”
“The data presented at EAHAD are promising, with 8 patients treated in a 4-dose cohort study, and the early data for the fourth dose cohort of 9.75e11 vg/kg suggests the potential to deliver FIX activity between 70-150%, the upper part of the normal range,” added Chris Hollowood, Executive Chairman of Freeline.
The study, a Phase 1/2, multi-centre, dose-finding, open-label trial, assesses the safety and clinical impact of systemic administration of single doses of FLT180a. The program aims to achieve normal FIX activity levels (50-150%), which would ensure that patients are free of the need for FIX concentrates and can mount a normal haemostatic response following inflammation, trauma or surgery. Participants were adult males with severe or moderately severe Haemophilia B with severe bleeding phenotype and no neutralising antibodies to AAVS3. Laboratory FIX activity values were measured with a one-stage assay (FIX:C). Patients were treated across 4 different dose cohorts to help identify the optimal dosing level in order to achieve FIX activity levels in the ‘normal’ range. A prophylactic immunosuppression regimen was started a minimum of 3 weeks post administration to modulate AAV vector related ALT rises and maintain gene expression. The immunosuppression regime has evolved across the dose cohorts to optimise a prophylactic regimen that results in consistent expression levels.
The Freeline FLT180a programme uses the company’s proprietary AAVS3 capsid and a gain of function variant of human factor IX (FIX). The B-AMAZE trial is being conducted in collaboration with UCL.
Freeline is a privately-held clinical-stage biotechnology company focused on AAV based gene therapy targeting the liver. Our vision is to create better lives for people suffering from chronic systemic diseases using the potential of gene therapy as a one-time curative treatment. Freeline is headquartered in the UK and has operations in Germany and the US.
About Haemophilia B
Haemophilia B is an inherited, X-linked disease characterized by spontaneous and prolonged bleeds in all tissues, including the joints, muscles and central nervous system. Haemophilia B is caused by mutations of the F9 gene encoding for coagulation factor IX (FIX) which plays an essential role in normal blood coagulation. Manifestations of Haemophilia can have lasting effects e.g., chronic arthropathy, life-threatening soft tissue bleeds, and CNS haemorrhages which can prove fatal. The life expectancy for Haemophilia B patients receiving treatment is 63-75 years dependent on severity of disease, and just 11 years for those without access to treatment.
Current treatment is aimed at preventing and treating bleeds through frequent intravenous infusions of Factor IX thus replacing the missing coagulation factor. Prophylactic use of FIX infusions reduces the number of bleeding episodes however due to the low FIX levels achieved and the peaks and troughs of FIX levels, the risk of development of arthropathy persist and patients are at continued risk of serious, even fatal bleeds e.g. because of trauma.