Two-year Follow Up of FLT201 Gene Therapy in Adults with Gaucher Disease Type 1

Описание: Ida Vanessa D. Schwartz, MD, PhD, HCPA, Professor of Genetics at the Federal University of Rio Grande do Sul, discusses two-year follow up from GALILEO-1 of FLT201 gene therapy in adults with Gaucher disease type 1 (GD1).

Gaucher disease refers to a group of inherited metabolic diseases in which harmful amounts of lipids accumulate in various cells and tissues in the body. Signs and symptoms vary widely among affected individuals and may include skeletal disorders, hepatosplenomegaly, liver malfunction, anemia, low platelet counts, bone problems, and neurological problems. There are different types of Gaucher disease classified according to specific features and severity, GD1 being the most common. It is caused by genetic changes in the GBA gene.

FLT201 is an investigational AAV gene therapy for GD1, comprising of a proprietary, liver-tropic capsid (AAVS3), with a unique transgene encoding GCase85, a novel engineered variant of β-glucocerebrosidase (GCase) under control of a liver-specific promoter. The treatment is designed to deliver continuous, durable endogenous expression of GCase85, eliminating the need for chronic treatment with enzyme replacement therapy (ERT) or superficial radiation therapy (SRT).

The GALILEO-1 clinical trial is the first-in-human study of FLT201, which enrolled six adults with GD1 on stable treatment with either ERT or SRT for at least two years prior to enrollment. Patients received a single IV infusion of FLT201 at a dose of 4.5 x10^11 vg/kg and follow-up duration ranged from 20 to 29 months. All patients are currently enrolled in the long-term follow-up study, GALILEO-2.

Four participants discontinued ERT/SRT following administration of FLT201 and remained off their background therapy. In these patients, FLT201 was observed to provide durable long-term GCase85 expression with cross-correction of peripheral blood leukocytes. Maintenance or improvement of hemoglobin and platelet count, stability in liver and spleen volumes, and clearance of lyso-Gb1 has been sustained or further reduced. Improvements were seen in one or more efficacy assessment in all four patients.

FLT201 administration was well-tolerated in all patients with no infusion-related reactions reported. The overall safety profile is favorable, with no treatment-related serious adverse events and only mild transient ALT elevations considered related to therapy were observed.

Chapters:
Introduction 00:00
Gaucher Landscape Overview 00:38
FLT201 Gene Therapy 1:58
Study Results 3:21
Next Steps 5:25
Take Home Message 5:52