The first patient in a Phase 1/2 clinical trial of Fabry disease gene therapy candidate FLT190 has been dosed.

Enrollment is ongoing at the Royal Free Hospital, in London, U.K. More information and contacts are available here.

Fabry disease iscausedby a faulty GLAgene, which provides instructions to make an enzyme called alpha-galactosidase A (alpha-GAL A). When mutated, this gene leads to abnormal alpha-GAL A function, which results in the build-up of lipids (fatty molecules) known as globotriaosylceramide (Gb3) and globotriaosylsphingosine (LysoGb3) that can damage the heart, kidneys, or liver.

Freelines FLT190 is a gene therapy that uses an adeno-associated virus (AAV8) a harmless virus that does not cause disease or infection as a vehicle to deliver a healthy copy of the GLAgene in the hopes it will induce the production of normal alpha-GAL A. In contrast to the regular infusions of enzyme replacement therapy (ERT), this gene therapy is designed to be given in a single dose.

The international, multi-center MARVEL1 study (NCT04040049) will primarily study the safety of FLT190 in up to 12 adult male patients with classic (type 1) Fabry disease, as well as whether it results in continuous production of high levels of alpha-GAL A. Other goals include clearance of Gb3 and LysoGb3, alterations in kidney and skin biopsies, renal and cardiac function, assessing immune responses, and quality of life.

After taking FLT190 via slow intravenous infusion, participants will be monitored for nine months at outpatient visits, and then enter a long-term follow-up period. Both previously and untreated patients will be included, although in two separate parts dose escalation and dose expansion.

MARVEL1 is the first trial of an AAV-based gene therapy for Fabry disease, according to the company. The trial is estimated to end by March 2021.

The initiation of this clinical study is an important event for the patient community. I am hopeful that the promising preclinical data will translate into long term benefit for patients with Fabry [disease], Derralynn Hughes, MD, PhD, said in a press release. Hughes isa Fabry disease expert and senior lecturer at Royal Free Hospital.

Preclinical results in a mouse model of the disease revealed that a single injection of FLT190 into the blood led to a sustained increase of more than 1,000-fold in alpha-Gal A levels, compared to healthy mice. The levels of Gb3 were reduced markedly in the kidney, spleen and heart, as were those of LysoGb3, which have been suggested as anaccurate biomarker to diagnose and track Fabry disease. No adverse side effects were found.

Chris Hollowood, Freelines executive chairman, said that starting MARVEL1 and dosing the first patient is a significant milestone for the company.Continuous high expression of [alpha-GAL A] holds the potential for better treatment outcomes than is seen with ERT, the current standard of care. We believe we can access high expression at relatively low doses.

Besides Fabry disease, Freeline also is testing its AAV technology in hemophilia B, in which a Phase 2/3 trial (NCT03641703) is evaluating whether the potential gene therapy FLT180a is safe and provides long-term production of the clotting protein missing in these patients (factor IX).

These innovative gene therapies have the potential to change patients lives, Hollowood said.

Jos is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimers disease.

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First Patient Dosed in Trial of Fabry Gene Therapy Candidate FLT190 - Fabry Disease News