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 uses a modified and harmless liver-directed adeno-associated virus to deliver to cells a healthy version of the GLA gene, which provides the instructions to produce Gal A and is mutated in Fabry patients.
By providing a working GLA copy, the one-time therapy is expected to restore Gal A levels, and thereby prevent the disease-characteristic toxic accumulation of fatty molecules — Gb3 and Lyso-Gb3 — that can damage the heart, kidneys, and liver.
Because the symptoms of Fabry disease appear in childhood, it may be necessary to treat patients before symptoms lead to irreversible organ damage. A gene therapy like FLT190 may not be able to reverse existing damage, though it might prevent the appearance of new symptoms or further damage.
FLT190 in clinical trials
Research conducted in animal models of Fabry disease using gene therapy has produced promising results.
A Phase 1/2 clinical trial (NCT04040049), called MARVEL1, is testing the safety and effectiveness of varying doses of FLT190 in up to 15 men with classic Fabry disease, which is associated with total or near-total absence of working Gal A.
Four doses are planned for evaluation in the study’s first phase: 7.5×1011, 1.5×1012, 4.5×1012, and 1.5×1013 vector genomes (vg) per kg of body weight. FLT190’s optimal dose will then be tested in the trial’s second phase.
Patients are given a single, slow intravenous (IV) infusion of FLT190 and then monitored for nine months. Freeline reported dosing its first study participant in September 2019, and a second patient in November 2021; both treated with a low therapy dose. MARVEL1 was affected by the COVID-19 pandemic starting in 2020 and the restrictions it required.
FLT190 was designated an orphan drug in both the U.S. and Europe for the treatment of Fabry disease. This designation is meant to accelerate the therapy’s development and review by providing regulatory support and financial incentives, most notably a market exclusivity period (of seven years in the U.S. and 10 years in Europe) if the medication is approved.
Last updated: Mar. 23, 2020
Fabry Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.