Freeline doses patient in first Fabry Disease AAV gene therapy trial globally

Published 12 Sep 2019

Freeline, a biotechnology company focused on developing curative gene therapies for chronic systemic diseases, today announced dosing of the first patient in its MARVEL1 study, a multi-centre Phase 1/2 clinical trial of its liver-directed AAV gene therapy for Fabry Disease.

The MARVEL1 study is the first clinical-stage adeno-associated virus (AAV) gene therapy study globally for Fabry Disease. The programme leverages Freeline’s proprietary gene therapy platform, including its novel capsid, which has already shown clinical benefit for Haemophilia B patients.

Fabry disease is a type of lysosomal storage disorder in which certain fatty molecules are not properly metabolised. Patients have a genetic mutation which leads to a deficiency of α-galactosidase A enzyme (αGLA) resulting in an accumulation of lipids, such as globotriaosylceramide (Gb3) and globotriaosylsphingosine (LysoGb3), throughout the body. This can cause highly debilitating progressive multi-organ disease.

It is estimated that Fabry Disease affects one in every 40,000* people. It is currently treated by  enzyme replacement therapy (ERT), which requires regular and expensive infusions. The MARVEL1 study aims to deliver a replacement copy of the missing gene to the liver, which will then produce continuous high levels of αGLA, offering the potential for therapy with a single treatment.

MARVEL1 is a multi-centre, international, dose-escalating Phase 1/2 study in adult males with classic Fabry Disease. The study is focused on assessing the safety of FLT190, and its ability to lead to continuous high levels of αGLA production. In addition to safety, endpoints in the study include clearance of Gb3 and LysoGb3 from the plasma, changes in renal and skin biopsies, renal and cardiac function, GLA immune response, viral shedding and quality of life.

Freeline published preclinical data on its Fabry programme in February 2019 at the WORLD Symposium in Orlando and presented further data in May 2019 at the Update on Fabry Disease in Prague, showing that a single dose of its liver-directed AAV gene therapy was able to correct disease in Fabry knockout mice. Freeline has shown long-term follow-up of sustained levels of GLA activity in Fabry knock-out mice and significant reductions of Gb3 in plasma and urine as well as the key disease tissues of kidney and heart, with no adverse effects being observed.

Prof. Derralynn Hughes, Royal Free Hospital, London, UK

“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.” 

“The initiation of our MARVEL1 study and dosing of the first patient is a significant milestone for Freeline,” said Chris Hollowood, Executive Chairman of Freeline. “Continuous high expression of alpha GLA 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. With two programmes in the clinic on a common proprietary gene therapy platform, Freeline are building a leading systemic gene therapy company using next-generation AAV technology. These innovative gene therapies have the potential to change patients’ lives.” 

*Fabry Support & Information Group