Freeline Therapeutics Holdings plc reported positive initial safety, tolerability and enzyme activity data from the ongoing Phase 1/2 GALILEO-1 trial evaluating FLT201, its adeno-associated virus (AAV) gene therapy candidate, in Gaucher disease. Gaucher disease is a debilitating genetic disorder in which a deficiency of the GCase enzyme leads to a buildup of harmful substrates, causing symptoms including enlarged spleen and liver, low blood counts, bone pain and reduced lung function. In addition to demonstrating a favorable safety and tolerability profile, data from the first two patients in GALILEO-1 show that a single infusion of FLT201 led to several hundred-fold increases in GCase activity in plasma and normalization of GCase activity in leukocytes. The data reported include assessments of safety, tolerability and GCase activity from the first two patients in GALILEO-1, which is a first-in-human, international, multicenter Phase 1/2 dose-finding study in people with Gaucher disease Type 1. Both patients were treated with a dose of 4.5x1011 vg/kg and have successfully come off their prior therapies. As of the September 27 data cutoff, the data demonstrated: Favorable safety and tolerability, with no infusion reactions and no serious adverse events as of 13 weeks post-dosing for patient 1 and six weeks post-dosing for patient 2. All treatment-related adverse events were Grade 1 and resolved without intervention.
No elevations in liver transaminase levels during the same time periods. Alanine-transaminase (ALT) and aspartate-transaminase (AST) levels remained in the normal range in both patients. Robust increases in plasma GCase levels. Patient 1 showed a nearly 700-fold increase over baseline to more than 70 µmol/L/h as of 12 weeks post-dosing. Patient 2 showed a similarly robust response, with a greater than 300-fold increase over baseline to approximately 30 µmol/L/h as of four weeks post-dosing. Normal plasma GCase levels range from 0.3 to 1.2 µmol/L/h (mean: 0.58 µmol/L/h). Normalization of leukocyte GCase activity, demonstrating cellular uptake of GCase from the plasma. Leukocyte GCase activity reached normal levels in patient 1 within four weeks of dosing and remained normal as of the last measurement. Similarly, leukocyte GCase activity in patient 2 reached normal levels within four weeks of dosing. Leukocytes are validated markers for broad cellular uptake in Gaucher disease. Both patients had normal hemoglobin levels at baseline and have remained in the normal range at each weekly assessment, including those taken after coming off enzyme replacement therapy or substrate replacement therapy. Given the compelling safety profile and robust enzyme activity at the 4.5x1011 vg/kg dose, a third patient has been scheduled for dosing in this first cohort to gather additional data before deciding whether to continue at the current dose or explore a higher dose. Three additional study patients have been identified and are in the process of being scheduled for dosing.