Freeline presents preclinical data and phase 1/2 study design of the FLT190 AAV gene therapy for Fabry Disease
- Category: DNA RNA and Cells
- Published on Wednesday, 29 May 2019 10:16
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May 28, 2019 I Freeline, a biotechnology company focused on developing curative gene therapies for chronic systemic diseases, presented pre-clinical data of FLT190, a novel proprietary AAV gene therapy to treat Fabry Disease at the 6th Update on Fabry Disease in Prague, Czech Republic.
Fabry mice (GLA knockout) received a single dose of ssAAV8-FRE1-GLAco (FLT190 pseudotyped with AA8 capsid). The first assessment of GLA levels made at four weeks after dosing showed levels up to 1061-fold higher compared to wild-type mice. These GLA levels were maintained throughout the follow up period, up to 98 days after dosing. Importantly, this single administration led to significant and durable reductions in Gb3 storage levels in the heart and kidney, thus demonstrating reduction of this toxic metabolite in important organs frequently affected by Fabry Disease. No adverse clinical signs or toxicity associated with high expression of α-GLA in the liver or increased plasma exposure to GLA were observed in the study.
Freeline also presented the study design for MARVEL1, the Phase 1/2 clinical study of FLT190 in patients with Fabry Disease. This study investigates the safety of FLT190, a new gene therapy using the Freeline proprietary AAVS3 capsid. In addition, the study will investigate the potential of FLT190 in treating the signs and symptoms of Fabry Disease following a single administration, including e.g. αGLA activity levels, Gb3/Lyso-Gb3 clearance, changes in Gb3 in renal and skin biopsies, renal and cardiac function, GLA immune response, viral shedding and quality of life. The study is currently recruiting at two sites in Europe.
Anne Prener, Chief Executive Officer of Freeline said:
“Our preclinical data are very encouraging, demonstrating clear evidence of the therapeutic potential of FLT190 in treating Fabry Disease.”
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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 Fabry Disease:
Fabry Disease is an inherited, X-linked disease characterized by the progressive accumulation of glycosphingolipids in lysosomes throughout the body. It is caused by mutations in the gene encoding of the α-galactosidase A enzyme (GLA) responsible for the breakdown of globotriaosylceramide (Gb3), a type of glycosphingolipid.The condition ranges from mild to severe and may appear anytime from childhood to adulthood.
The progressive accumulation of Gb3 leads to organ damage, major disability and often early mortality. Symptoms and signs include neuropathic pain, impaired sweating, gastrointestinal symptoms, renal failure, heart disease and increased risk of stroke. Current treatment consists of enzyme replacement therapy and chaperone therapy to temporarily clear Gb3 accumulation and alleviate symptoms.