Gene Therapy Increases GCase Activity in Patients With Gaucher


The updated data are from the first 2 patients treated in the phase 1/2 GALILEO-1 trial of FLT201.

Freeline Therapeutics has reported data including significant increases in plasma GCase activity in patients with Gaucher disease treated with FLT-201 adeno-associated virus (AAV) gene therapy in the phase 1/2 GALILEO-1 trial (NCT05324943).1

"These initial clinical data are very compelling,” investigator Pilar Giraldo, MD, PhD, hematologist, Spanish Foundation for the Study and Therapy of Gaucher Disease, Quirónsalud Hospital – Zaragoza, said in a statement.1 “While existing therapies have had a significant impact on the disease, many patients continue to experience symptoms and current therapies come with a heavy lifelong treatment burden. People with Gaucher disease deserve better treatment options. FLT201 represents a promising new approach as a one-time investigational gene therapy, and based on the emerging clinical data, I am excited about its potential.”

The data are from the first 2 patients treated in the trial with a dose of 4.5x1011 vg/kg FLT-201 who have both successfully come off their prior therapies. As of September 27, both patients showed a favorable safety and tolerability profile, with no infusion reactions for serious adverse events (AEs). The patients have been followed up for 13- and 6-weeks post-treatment. AEs that occurred were grade 1 and resolved without intervention. There have been no elevations in liver transaminase levels.

“FLT201 is a highly differentiated gene therapy candidate for Gaucher disease with the opportunity to provide better outcomes for patients, while dramatically reducing the burden that comes with existing therapies,” Pamela Foulds, MD, chief medical officer, Freeline, added.1 “The magnitude of the increases in plasma GCase activity in the first two patients treated with FLT201, together with the normalization of GCase activity in cells, further strengthen our belief in its therapeutic potential. Given the strong response and clean safety and tolerability to date, we have decided to treat a third patient at this dose rather than a higher dose as initially planned.”

READ MORE: Freeline Goes All in on Gaucher Disease

Both patients also showed robust increases in plasma GCase levels, with patient 1 having a nearly 700-fold increase from baseline to over 70 μmol/L/h as of 12 weeks post-dosing and patient 2 having over a 300-fold increase from baseline to around 30 μmol/L/h as of 4 weeks post dosing, as compared with the normal GCase range of 0.3 to 1.2 μmol/L/h (mean: 0.58 μmol/L/h).1 Both patients had and continue to have normal hemoglobin levels, prior to the study and after discontinuing enzyme replacement. A third patient has now been scheduled for dosing in the first cohort and 3 additional patients are being scheduled for dosing.

“Our goal at Freeline is to unlock the true potential of gene therapy by optimizing every component of our product candidates,” Michael Parini, chief executive officer, Freeline, added.2 “FLT201 exemplifies that approach. It leverages our proprietary capsid designed to deliver high expression at low doses and our novel GCase variant engineered to overcome the short half-life of wildtype GCase. Our preclinical data for FLT201 show robust increases in plasma GCase, which is then taken up by disease-affected tissues, clearing harmful substrate more effectively than the existing standard-of-care. These clinical data show the preclinical data are starting to translate, and we are committed to expeditiously advancing FLT201.”

FLT201 is Freeline’s only clinical gene therapy candidate in the pipeline after it dropped its hemophilia and Fabry disease programs in late 2022 and early 2023, respectively.3 Only 2 patients were treated in the phase 1/2 MARVEL-1 clinical trial (NCT04040049) of the FLT190 program for Fabry, while the phase 1/2 B-AMAZE trial (NCT03369444) of the FLT180a program for hemophilia A showed that only half of the 10 treated patients had Factor IX in the normal range as of last follow-up.

1. Freeline reports positive initial clinical data from first cohort of phase 1/2 GALILEO-1 trial of FLT201, its novel gene therapy candidate, in Gaucher disease. News release. Freeline Therapeutics. October 4, 2023.
2. Freeline Reports Full Year 2022 Financial Results and Provides Corporate Update. News release. April 4, 2023.
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