- Updated FLT180a data in the B-AMAZE study in severe Haemophilia B patients demonstrated the potential for sustained normal FIX activity levels -
- Additional data were presented in 5 poster presentations -
LONDON, July 13, 2020 (GLOBE NEWSWIRE) -- Freeline, a clinical stage, Adeno-Associated Virus (AAV) based gene therapy company with the ambition of transforming the lives of patients suffering from inherited systemic debilitating diseases, today announced new data on its AAV gene therapy product candidate, FLT180a, in severe Haemophilia B patients at the International Society on Thrombosis and Haemostasis (ISTH) 2020 Congress. The data presented in an oral presentation by Professor Pratima Chowdary of the Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital UK and UCL Cancer Institute, and Principal Investigator for the study, demonstrated with data up to two years for the earliest cohort, that a dose of between 7.5e11 and 9.75e11 vg/kg has the potential to create durable Factor IX (FIX) activity levels in the normal range in patients with severe Haemophilia B.
“We are delighted to report additional data from the first 10 patients treated in our Haemophilia B trial,” said Theresa Heggie, CEO of Freeline. “These data build on previously reported data which suggest that FLT180a has the potential, using relatively low doses, to create durable FIX activity levels in the normal range in patients with severe Haemophilia B and provide a functional cure.”
“The clinical data shows the progress we have made in achieving Factor IX levels in the normal range for people with severe or moderately severe Haemophilia B, which has the potential to markedly improve their quality of life,” added Professor Pratima Chowdary of the Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital, and UCL Cancer Institute, UK.
Reportable data1 is available for 10 patients who have been treated with FLT180a across 4 dose cohorts. All patients had severe or moderate Haemophilia B with baseline FIX activity levels prior to gene therapy of 2% or less. The first dose cohort (2 patients) has follow-up over 104 weeks, the next 2 dose cohorts (2 patients in each) have data available over 26 and 52 weeks, respectively. The most recent dose cohort (4 patients) has FIX activity level readings available at 3 weeks, with 2 of those patients also having data available at 26 weeks.
Long term durability up to 2 years was seen in the 2 patients in the lowest dose cohort (4.5e11 vg/kg) with an average FIX level activity at 52 and 104 weeks, both of 38%, which are levels commonly associated with mild Haemophilia B. There was no evidence of transaminitis and transient steroid induced increases in FIX activity levels were observed in both patients.
Durable FIX activity levels in the normal range were seen at doses of 7.5e11 and 9.75e11 vg/kg. Two patients received a dose of 7.5e11 vg/kg and at 3 weeks each had comparable expression at 25.5% (26% and 25%). At week 26, one of the 2 patients experienced a rise in alanine aminotransferase (ALT)2 that was followed by a decline in expression. The other patient went on to have a normal FIX activity level of 60% at week 52. In addition, 4 patients received a dose of 9.75e11 vg/kg and at week 3 their respective FIX activity levels were 136%, 82%, 73% and 105%. Two patients from this dose cohort have now reached 26 weeks post-infusion and have shown FIX activity levels of 139% and 57%; the latter case in a patient who experienced an increase in ALT which resulted in a reduction in FIX expression. Two patients received a higher dose of 1.5e12 vg/kg. This was deemed by the Company to be a higher dose than required for the potential treatment of Haemophilia B. Average FIX expression at 26 weeks was 160%, including 1 patient with reduction in FIX expression following transaminitis. To date no bleeds have required supplemental FIX in any of our patients studied.
Freeline has continued to optimise its prophylactic immune management regimen throughout the trial, with an aim both to consistently control ALT levels to prevent loss of FIX expression. The current immune management regimen, using prophylactic corticosteroids and tacrolimus3, was implemented for the last three patients in the 9.75e11 vg/kg dose level.
Freeline also presented data on the FIX Padua variant and health economics from its AAV-based Haemophilia gene therapy platform in five poster presentations at the conference.
Further information
JW Communications
Julia Wilson
+44 (0) 7818 430877
juliawilsonuk@gmail.com
About Freeline
Freeline is a clinical-stage biotechnology company focused on AAV-based gene therapy targeting the liver. Its vision is to create better lives for people suffering from chronic, systemic diseases using the potential of gene therapy as a one-time treatment to provide a potential functional cure. Freeline is headquartered in the UK and has operations in Germany and the US.
About Haemophilia
Haemophilia is a genetic bleeding disorder where a protein made by the body to help make blood clot is either partly or completely missing. This protein is called a clotting factor. In Haemophilia A, there is a deficiency of the clotting Factor VIII (8) protein and in Haemophilia B, there is a deficiency of the clotting Factor IX (9) protein. Haemophilia mainly affects boys and men; however, women can be ‘carriers’ of the affected gene and may experience symptoms. Haemophilia A is the most common type of Haemophilia affecting about one in every 5,000 males, while Haemophilia B affects about one in every 30,000 males. Haemophilia is classified as mild, moderate or severe, depending on the level of clotting Factor VIII or IX in the blood and is diagnosed through blood tests.
About FLT180a
The Freeline Haemophilia B programme, FLT180a, uses a synthetic AAVS3 capsid and a gain of function variant of human factor IX (FIX). The therapy is currently being studied in a Phase 1/2 trial, B-AMAZE, with the goal of normalising FIX activity in patients with moderate and severe Haemophilia B.
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1 As at cut-off date of 15 June 2020
2 Alanine aminotransferase (ALT) is an enzyme that is predominantly found in the liver. Damage to liver cells can lead to release of more ALT in the bloodstream and therefore ALT levels in the blood can be used as a marker of liver damage or toxicity, and risk of loss of FIX expression.
3 An immunosuppressive drug widely used in transplantation surgery.