FRLN - 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 | Benzinga
Robust increases of up to 700-fold over baseline in plasma GCase enzyme activity in first two patients treated with FLT201
Normalization of leukocyte GCase in both patients demonstrates cellular uptake from plasma
FLT201 has been well tolerated, with no serious adverse events
Company to host conference call today at 8 a.m. ET
LONDON, Oct. 04, 2023 (GLOBE NEWSWIRE) -- Freeline Therapeutics Holdings plc (NASDAQ:FRLN) today 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.
"These initial clinical data are very compelling," said Pilar Giraldo, M.D., Ph.D., hematologist at the Spanish Foundation for the Study and Therapy of Gaucher Disease, Quirónsalud Hospital – Zaragoza, and an investigator in the GALILEO-1 trial. "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."
"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," said Pamela Foulds, M.D., Freeline's Chief Medical Officer. "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."
"Our goal at Freeline is to unlock the true potential of gene therapy by optimizing every component of our product candidates," said Michael Parini, Freeline's Chief Executive Officer. "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."
Positive Initial Clinical Data for FLT201
The data reported today 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 ...