Freeline announces new data from GALILEO-1 trial of FLT201

Freeline announced that new clinical data from its ongoing Phase 1/2 GALILEO-1 trial of FLT201, its adeno-associated virus, or AAV, gene therapy candidate for Gaucher disease, show a substantial reduction of glucosylsphingosine levels in the blood of the first patient treated with FLT201. Lyso-Gb1 is a well-established biomarker of clinical response in Gaucher disease, with reductions in lyso-Gb1 correlating with positive clinical outcomes. These data are being highlighted in an oral presentation at the European Society of Gene & Cell Therapy, or ESGCT, 30th Annual Congress held in Brussels, Belgium. The presentation at ESGCT will include updated data on safety, tolerability, and GCase activity, as well as new data on lyso-Gb1, hemoglobin and platelet levels, from the first two patients dosed in GALILEO-1, 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 4.5×1011 vg/kg and have successfully come off their prior therapies. A third patient was dosed in the same cohort earlier this month; only safety, tolerability and liver transaminase data were available for patient 3 as of the data cutoff. As of the October 13 data cutoff, the data demonstrated: Favorable safety and tolerability, with no infusion reactions and no serious adverse events as of 16 weeks post-dosing for patient 1, nine weeks post-dosing for patient 2, and one week post-dosing for patient 3. All treatment-related adverse events were mild and resolved without intervention. Alanine-transaminase, or ALT, and aspartate-transaminase, or AST, levels remained in the normal range for all patients during the same time periods. Robust increases in plasma GCase levels. Patient 1 showed an approximately 700-fold increase over baseline to more than 70 micromol/L/h as of 12 weeks post-dosing. Patient 2 showed a similarly robust response, with an approximately 450-fold increase over baseline to more than 40 micromol/L/h as of six weeks post-dosing. Normal plasma GCase levels range from 0.3 to 1.2 micromol/L/h. Normalization of leukocyte GCase activity, indicating cellular uptake of GCase. Leukocyte GCase activity reached normal levels in patient 1 and patient 2 within four weeks of dosing and remained normal through week 14 and week 8, respectively. Leukocytes are validated markers for broad cellular uptake in Gaucher disease. Reduction in DBS lyso-Gb1 levels in patient 1 to approximately 60 ng/mL as of 12 weeks post-dosing from more than 100 ng/mL at the patient’s initial assessment. Only one post-dosing assessment was available for patient 2 as of the data cutoff. Patients 1 and 2 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.