Gaucher Disease Type 1 Gene Therapy Shows Promising Initial Data


The therapy has been well-tolerated in the first 3 participants which also showed GCase expression in the plasma.

FLT201 gene therapy has shown a favorable safety profile and prompted robust glucocerebrosidase (GCase) expression in the plasma and normalized levels in cells of patients with Gaucher disease type 1 (GD1).

Updated data from the GALILEO-1 clinical trial (NCT05324943) evaluating FLT201 were presented by Ozlem Goker-Alpan, MD, founder and chief medical officer, Lysosomal and Rare Disorders Research and Treatment Center, at the 30th Annual Congress of the European Society of Gene & Cell Therapy (ESGCT), held October 24-27 in Brussels, Belgium.

“GCase deficiency leads to accumulation of glucocerebroside throughout the body, including in macrophages and the reticuloendothelial system. GD1 is characterized by hepatosplenomegaly, anemia, thrombocytopenia, bone disease and pulmonary involvement without neurological involvement,” Goker-Alpan said during her presentation. “Approved therapies for GD1 are enzyme replacement therapy (ERT) and substrate reduction therapy (SRT).”

READ MORE: Gaucher Disease Type 1 Gene Therapy Trial Proceeds to Dose Second Cohort

GALILEO-1 is a first-in-human, open-label study evaluating the safety and tolerability of FLT201 in patients with GD1 receiving ERT or SRT. So far, 3 participants have received the low dose of 4.5E11 vg/kg FLT201. The trial may expand to a mid-dose cohort of 1.3E12 vg/kg, a higher dose of 3.9E12 vg/kg, and a highest dose of 1.1E13 vg/kg with 2-3 patients in each additional cohort.

“Continuous endogenous GCase production may address aspects of the disease that ERT cannot. Transient elevations in plasma and cellular GCase lead to incomplete systemic distribution and short-lived presence in cells. FLT201 may lead to steady, constant GCase expression in plasma and within all cell types tested,” Goker-Alpan said. “Near complete prevention of substrate accumulation in the liver, spleen, bone marrow, lung was seen in non-clinical studies at doses of 2x1011 and 2x1012 vg/kg.”

With a data cutoff of October 13, which represents follow-up of 1, 9, and 16 weeks after dosing, the gene therapy has shown a favorable safety profile in the 3 participants. The infusions were well-tolerated with no serious adverse events (AEs), and alanine transaminase and aspartate transaminase elevations below the upper limit of normal. There were 2 mild, grade 1 AEs that spontaneously resolved and mild-to-moderate AEs related to corticosteroids and tacrolimus and consistent with their safety profiles.

Clinical Takeaways

  • Initial data from the GALILEO-1 clinical trial evaluating FLT201 gene therapy in Gaucher disease type 1 (GD1) showed it to be well-tolerated, with a favorable safety profile.
  • FLT201 may offer advantages over existing therapies, as it induces steady GCase expression in plasma and all cell types, potentially preventing substrate accumulation in critical organs.
  • The gene therapy prompted GCase expression in the plasma, and led to the normalization of intracellular GCase levels, with early data suggesting the potential for meaningful improvements in outcomes for GD1 patients.

FLT201 induced GCase expression in plasma, followed by normalization of intracellular GCase levels. The 2 participants with longer follow-up had stable hemoglobin and platelet counts. Early lyso-Gb1 data suggests a positive trend. The first participant stopped ERT at week 11 and the second stopped SRT at week 5.

"GCase-variant 85, produced by FLT201, is more stable than recombinant human GCase providing continuous tissue access to the needed enzyme," Goker-Alpan said." Early clinical data shows a favorable safety profile with robust GCase expression in plasma and normalization of levels within the cell. Early lyso-Gb1 data suggests potential for meaningful improvements in outcomes."

Goker-Alpan O, Whittaker A. Results from GALILEO-1, a first-in-human clinical trial of FLT201 gene therapy in patients with Gaucher disease Type 1.
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