AAV Gene Therapy in Patients With Gaucher Disease

Reena Sharma, MD, Salford Royal Hospital and University of Manchester, UK, discusses clinical data from a clinical trial testing an AAV gene therapy in patients with Gaucher disease.

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. It is caused by genetic changes in the GBA gene.

The GALILEO-1 study is a phase 1/2, a first-in-human, international, multicenter dose-finding study clinical trial testing the safety, tolerability, and efficacy of FLT201 in adult patients with Gaucher disease. FLT201 is an investigational adeno-associated virus (AAV) gene therapy that delivers GCase85, a longer-acting version of the deficient enzyme in Gaucher. The goal is to stop disease progression, reduce or eliminate symptoms, and allow patients to come off lifelong treatments.

Clinical data from the GALILEO-1 study was recently presented at the European Society of Gene and Cell Therapy (ESGCT) Annual Congress. Six patients were treated with a single infusion of FLT201 at a 4.5e11 vg/kg dose. While all six patients are included in the safety analysis, one was excluded from the efficacy analysis. Safety and tolerability of the treatment was observed to be favorable with only mild to moderate adverse events.

Additionally, durable reductions were seen in lyso-Gb1 levels, ranging from 42% to 96%, in patients with high levels despite prior treatment. Improvements were seen in bone marrow burden illustrating FLT201’s ability to penetrate deeper tissues. Spleen and liver volume were also improved or maintained as well as maintenance of hemoglobin levels and platelet counts.

Further data from the trial is expected in the first half of 2025 with plans to initiate a phase 3 trial.