How does FLT190 work?
Fabry disease is caused by mutations in the GLA gene, which encodes for an enzyme called alpha-galactosidase A. This enzyme is responsible for breaking down waste products in a cellular compartment called the lysosome. Mutations in GLA result in the production of non-functional alpha-galactosidase A enzyme. This leads to the buildup of fatty cellular wastes called globotriaosylceramide within the cells, which causes the symptoms of Fabry disease.
FLT190 is a type of gene therapy that aims to compensate for the mutated GLA gene. It uses an inactivated virus, which does not cause disease or infection, to introduce a healthy copy of the GLA gene into the patient’s genome. It is hoped that the introduced gene can be used to produce normal alpha-galactosidase A enzyme, treating the disease.
This type of approach is still very new and it is unclear what dosage of the virus will be necessary to achieve normal levels of enzyme production. It is also unclear whether a single treatment would be sufficient for a patient’s lifetime, or whether multiple treatments would be necessary.
Another consideration is that the symptoms of Fabry disease appear in childhood, and it may be necessary to treat patients with FLT190 before symptoms lead to irreversible organ damage, such as kidney disease, in order to be effective. Gene therapy may not be able to reverse the damage already caused by Fabry disease, though it should prevent the appearance of new symptoms.
FLT190 in clinical trials
Research conducted in animal models of Fabry disease using gene therapy has produced promising results.
Freeline has initiated a Phase 1/2 clinical trial (NCT04040049), nicknamed MARVEL1, for adult male patients with Fabry disease. The study is currently recruiting up to 15 participants at locations in Italy, Norway, and the United Kingdom. In the study, patients will be given a single, slow intravenous (IV) infusion of FLT190 and then will be monitored periodically for 9 months. Freeline reported dosing its first participant in the study in September 2019. The trial is estimated to be completed in December 2021.
FLT190 received Orphan Drug Designation from the European Commission (EC) in March 2020 which can help it get approved faster.
Last updated: Mar. 23, 2020
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