Freeline Therapeutics recently announced plans to progress dose escalation for its Phase I/II trial for FLT190, an adeno-associated variant (AAV) based gene therapy for Fabry disease. The current position that Freeline has achieved with FLT190 places the company ahead of its direct competitors and into a strategic position to dominate the Fabry gene therapy landscape, provided it is able to continually produce high efficacy and safety data, says GlobalData, a leading data and analytics company.

Akash Patel, Pharma Analyst at GlobalData, comments: “Freeline’s preliminary data and confidence progressing dose escalation during 2021 will likely show single-dose, AAV-based therapies to be highly efficacious at treating lysosomal storage disorders, such as Fabry disease. AAV therapies have found an early position in the Fabry disease pipeline and require more clinical data to establish its likely market position and uptake.”

There are several AAV therapies that are currently at Phase I/II of clinical development in the Fabry disease market, as well as the wider lysosomal storage disease market. FLT190, however, is the first AAV-based therapy in the Fabry disease pipeline to demonstrate significant efficacy, with a near four-fold increase in α-GAL A activity achieved by the fourth week of its trial (0.3  1 ± 0.2 nmol/hr/ml). FLT190 aims to deliver a functional copy of its therapeutic gene galactosidase-α (GLA), which encodes for α-GAL A, into the liver from where it is secreted.

Two further AAV-based therapies identified on GlobalData’s Pharma Intelligence Center, Sangamo Therapeutics’ ST920 and 4D Molecular Therapeutics’ 4D-310, are set to produce preliminary data in late 2021. Both therapies also aim to show significant efficacy with single-dose administration and the preliminary data from the FLT190 trial demonstrates significant potential for these therapies.

A fourth gene therapy identified by GlobalData, Avrobio’s AVR-RD-01, has shown some promising preliminary data in a Phase I/II data, although it is a lentiviral vector therapy that is a ex vivo gene therapy. This therapy has produced a three-fold increase in α-GAL A enzyme activity in one patient at three months after dosing, and as sustained plasma Gb3 decrease in another patient at nine months after dosing. AVR-RD-01 is FLT920’s closest competitor in terms of clinical data released, although key opinion leaders (KOLs) interviewed to by GlobalData have indicated that its multiple stages of treatment mean it is unlikely to be popular with patients and physicians.

Patel concludes: “FLT190 is likely to revolutionise the treatment of Fabry disease over a patient’s lifeline, or even as a single-dose curative therapy, compared to the current bimonthly ERT regimen, and lead to Freeline Therapeutics becoming a leader in the AAV gene therapy space.”