Freeline Therapeutics has unveiled new clinical data from its ongoing Phase 1/2 GALILEO-1 trial of
FLT201, an adeno-associated virus (AAV) gene therapy candidate for
Gaucher disease. The data indicate significant reductions in glucosylsphingosine (lyso-Gb1), a key biomarker of clinical response, in patients with persistently high levels despite long-term treatment with existing therapies. Early signs of clinical improvement have also been observed in bone marrow burden and
fatigue.
Gaucher disease stems from a mutation in the
GBA1 gene, leading to a deficiency of the enzyme glucocerebrosidase (GCase). This enzyme deficit causes harmful substrates to accumulate in cells and organs, resulting in symptoms such as enlarged spleen and liver,
low blood counts,
bone pain, fatigue, and reduced lung function. FLT201 delivers an engineered version of the GCase enzyme (GCase85) with enhanced stability, designed to remain in cells longer, effectively clear substrates, and reach tissues less accessible by current treatments, including bone.
In a presentation at the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting, Freeline highlighted the Phase 1/2 GALILEO-1 trial data. The trial involves adult patients with
Gaucher disease Type 1 and is conducted internationally across multiple centers. The reported data cover four patients who have discontinued their previous treatments and have been followed up for 14 to 32 weeks post-dosing.
Key findings from the data include:
- Favorable safety and tolerability, with no serious adverse events or infusion reactions. Some patients experienced mild to moderate elevations in alanine-transaminase (ALT) levels, managed effectively with immune therapy.
- Robust and continuous expression of GCase in plasma, with clear evidence of cellular uptake indicated by GCase activity in leukocytes.
- Significant reductions in lyso-Gb1 levels in patients with previously high levels, and maintenance of low lyso-Gb1 levels in one patient with well-controlled levels prior to the trial.
- Maintenance and improvement of hemoglobin and platelet counts post withdrawal of enzyme replacement therapy (ERT) or substrate reduction therapy (SRT).
- Emerging data also demonstrated reductions in bone marrow burden and clinically meaningful improvements in fatigue for the first patient dosed, based on the Functional Assessment of
Chronic Illness Therapy (FACIT) fatigue scale.
FLT201 has been granted Regenerative Medicine Advanced Therapy (RMAT) designation by the FDA and Priority Medicines (PRIME) designation by the European Medicines Agency (EMA). These designations are intended to expedite the development and review processes for therapies addressing serious or life-threatening diseases with unmet medical needs.
Freeline also shared promising data from its Parkinson’s disease research program, leveraging the same long-acting engineered GCase enzyme as FLT201. This program focuses on a subset of Parkinson’s disease patients with GBA1 mutations, which greatly increase the risk of developing the disease and are associated with earlier onset and more severe symptoms. The findings showed that GCase85 exhibited significantly higher activity compared to the wildtype enzyme in both in vitro and in vivo studies, and effective distribution to target cells in the brain following direct injection using an AAV9 vector.
FLT201 aims to offer a one-time treatment that can arrest disease progression, improve patient outcomes, and eliminate the need for lifelong therapy. Preclinical studies demonstrated robust GCase expression and significant reduction of harmful substrates in key tissues, supporting the potential of this gene therapy to transform the treatment landscape for Gaucher disease.
In summary, Freeline Therapeutics' recent clinical data underscore the potential of FLT201 to provide substantial clinical benefits for patients with Gaucher disease, offering a promising alternative to current lifelong treatment regimens and laying the groundwork for further research into GBA1-linked Parkinson’s disease.
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