GALILEO-1: A Phase I/II Safety and Efficacy Study of FLT201 Gene Therapy for Gaucher Disease Type 1

Abstract

Gaucher disease type 1 (GD1), caused by mutations in the GBA1 gene, results in β-glucocerebrosidase (GCase) deficiency. Gene therapy is under investigation as a potential treatment option for patients with GD1. The investigational gene therapy FLT201 consists of an adeno-associated virus (AAVS3) encoding a novel GCase variant (GCase-85). Preclinical characterization of FLT201 showed promising results, with GCase-85 being more stable at physiological pH than wild-type GCase and delivered effectively to target tissues. Here, we describe the design of GALILEO-1, a first-in-human Phase I/II safety, tolerability and efficacy study of FLT201 gene therapy in adult patients with GD1. The study results will inform the decision to start a Phase III study of FLT201 in patients with GD1. Clinical Trial Registration: NCT05324943 ( ClinicalTrials.gov )

Advancements in Viral Gene Therapy for Gaucher Disease

“…The first (GALILEO-1), “A Gene Therapy Study in Patients with Gaucher Disease Type 1” (NCT05324943), conducted by Freeline Therapeutics, involves the administration of a liver-directed ssAAV to participants as a one-time intravenous infusion. The group made 37 GBA1 AAV constructs, which, when infused in mice with RC-04-26, resulted in the robust uptake of GCase by cells in spleen, bone marrow, and lung [ 98 ]. At this time, no results have been reported from the patient trial.…”

The Liver and Lysosomal Storage Diseases: From Pathophysiology to Clinical Presentation, Diagnostics, and Treatment

“…While the stable expression in the nervous system is the most important factor for treating neuronopathic GD, it is also desirable to express GBA1 systemically to treat pathology in visceral organs [ 72 ]. Currently, there are a few active gene therapy clinical trials for the treatment of GD [ 73 ]. Miranda et al reported promising results regarding liver-directed gene therapy in vitro and in vivo for the treatment of GD.…”

Novel gene therapy advances for treating primary immunodeficiency disorders – an update

“…FLT201 is an experimental gene therapy that utilizes AAVS3 containing a unique variant of GCase (GCase-85). FLT201 has shown promising preclinical results, GCase-85 demonstrating improved stability at physiological pH as compared to wild-type GCase along with efficient transport to tissues targeted 12 .…”