New Positive Data on FLT201 Gene Therapy for Gaucher Disease at ASGCT Meeting

Freeline Therapeutics has reported significant findings from its Phase 1/2 GALILEO-1 trial, which is testing FLT201, an AAV gene therapy for Gaucher disease. The new clinical data reveal substantial decreases in glucosylsphingosine (lyso-Gb1), a key biomarker for clinical response, in patients who had high levels even after years of treatment with existing therapies. Moreover, early clinical improvements were observed in bone marrow burden and fatigue, indicating the potential for FLT201 to enhance patient outcomes with a one-time treatment, as opposed to the ongoing treatments currently available.

Gaucher disease is a genetic disorder caused by a mutation in the GBA1 gene, leading to a deficiency in the glucocerebrosidase (GCase) enzyme. This deficiency results in a buildup of substrates in cells and organs, causing various symptoms such as enlarged organs, bone pain, and fatigue. FLT201 is designed to introduce a more stable version of the GCase enzyme (GCase85) that remains in cells longer, effectively clearing substrates and reaching tissues that are difficult for current treatments to access.

The GALILEO-1 trial is a first-in-human, international, multicenter study in adults with Gaucher disease Type 1. The latest data presented at the ASGCT 27th Annual Meeting in Baltimore, Maryland, included results from four patients who had stopped their previous treatments and were followed up for 14 to 32 weeks after receiving a single dose of FLT201.

The findings highlighted favorable safety and tolerability, with no infusion reactions or serious adverse events. The therapy showed robust and continuous expression of GCase in plasma, with cellular uptake of GCase from the plasma, as evidenced by leukocyte activity. Notably, patients with persistently high lyso-Gb1 levels prior to the trial experienced substantial reductions, and those with well-controlled levels maintained them post-treatment.

Furthermore, the emerging data from April 8, 2024, showed reductions in bone marrow burden and clinically meaningful improvements in fatigue levels in the first patient dosed. FLT201 has been granted the Regenerative Medicine Advanced Therapy (RMAT) designation by the FDA and Priority Medicines (PRIME) Designation by the EMA, which aims to expedite the development and review of therapies for serious or life-threatening diseases.

Freeline also announced promising data from its GBA1 Parkinson’s disease gene therapy program, which is leveraging the same GCase85 enzyme as FLT201. The research indicates that GCase85 has significantly higher GCase activity compared to the wildtype enzyme and can be effectively distributed to target brain cells when injected using an AAV9 vector.

The company is encouraged by the clinical data for FLT201 and is optimistic about extending the therapeutic potential of its GCase85 enzyme to genetically linked Parkinson’s disease patients with GBA1 mutations. Freeline Therapeutics is a clinical-stage biotechnology company dedicated to developing gene therapies for chronic debilitating diseases, with its headquarters in the UK and operations in the US.