New Medicines

Fabry's disease


New molecular entity
Freeline Therapeutics
Freeline Therapeutics

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Nov 21Freeline is engaging with regulatory authorities to update study protocols and trial design for FLT190 and expects to continue patient dosing in Q1 2022 following these updates. Freeline anticipates interim data readouts from the MARVEL-1 trial in 2022 [6].
May 20Granted orphan drug status in US [4].
Mar 20Granted orphan drug status in EU [3].


A next generation liver directed adeno associated virus (AAV) based gene therapy.
Anderson-Fabry disease is an X-linked recessive inborn error of glycosphingolipid metabolism caused by deficiency of alpha-galactosidase A. It is estimated to occur in 1 in 55,000 males in the classical form but the atypical variant may be more common [1].
Fabry's disease
Intravenous infusion

Trial or other data

Apr 22A long-term follow-up study is also underway (NCT04455230), and recruiting at the Royal Free Hospital in London [7].
Nov 21Freeline announces new data from its ongoing PhI/II MARVEL-1 dose-finding trial from patients one and two. Patient two was dosed at the lowest dose cohort of 7.5e11 vg/kg in June 2021 and experienced a sustained and durable response with an increase in expression of plasma α-galactosidase A (α-Gal A) to near normal levels, from 0.0nmol/hr/mL at baseline to an average of 3.9nmol/hr/mL from weeks 6 to 16 post-dosing. Thus far, the patient remains off enzyme replacement therapy (ERT). With respect to safety, the treatment was well-tolerated with no dose-limiting toxicities or serious adverse events (SAEs). As of the cutoff date, there were no adverse events higher than Grade 1 (mild). Patient Two has a history of cardiac disease and on routine weekly monitoring, an incidental finding of changes in cardiac markers, troponin-T and electrocardiogram (ECG), was observed, although the patient was asymptomatic. After evaluation, these findings were determined to be consistent with mild and transient myocarditis. Patient 2’s troponin-T has since reverted to baseline, and the ECG remained stable as of the cutoff date. Ventricular functioning in the heart has remained normal throughout. Patient Two has experienced no elevations in liver enzymes under our current immune management regimen, which has evolved in response to patient data in the hemophilia B and Fabry programs. The total vector genome (vg) dose Patient Two received was approximately 40% higher than Patient One due to differences in their weights. Patient Two saw a 400% increase in enzyme levels compared with Patient One. Long-term follow-up from Patient One shows durable response with plasma α-Gal A activity levels remaining elevated at two years post-dose and generally steady at an average of three times baseline. The patient had a subtherapeutic response with plasma α-Gal A at 0.8-1.3 nmol/hr/mL and restarted ERT at week six. Patient One has experienced no enduring clinical sequelae of the transient mild myocarditis episode previously reported in 2019. Ventricular functioning in the heart remained normal throughout with cardiac magnetic resonance imaging (MRI) showing no evidence of scarring on follow-up at one- and two-years post-dosing. An independent Data Monitoring Committee (DMC) conducted a comprehensive review of safety and efficacy data from the two patients dosed in the lowest dose cohort in the MARVEL-1 trial. The DMC has recommended that Freeline proceed with dosing a third patient in the first cohort at the same 7.5e11 vg/kg dose level with additional cardiac monitoring, which will be followed by an additional DMC meeting [6].
Feb 20Preliminary data from the PI/II MARVEL1 trial on the starting dose in a dose escalation study show that the infusion was well tolerated. A 3 to 4-fold increase in plasma αGLA activity was achieved by week 4 (0.3 → 1 ± 0.2 nmol/hr/ml) and sustained through the data cutoff at week 20 [5].
Feb 20PI/II MARVEL1 trial is recruiting [2].
Jul 19Freeline Therapeutics initiates the PI/II MARVEL1 trial to assess the safety and efficacy of FLT190, for the treatment of Fabrys disease (NCT04040049; FLT190-01). Besides safety, the study will explore the potential of FLT 190 in treating the signs and symptoms of Fabry´s disease, following a single administration, including αGLA activity levels, Gb3/Lyso-Gb3 clearance, changes in Gb3 in renal and skin biopsies, renal and cardiac function, GLA immune response, viral shedding and quality of life. The baseline-controlled, non-randomised, open-label, single-ascending dose study intends to enrol 15 adults in Italy, Norway, and the UK (at the Royal Free Hospital in London) Collection of primary outcome data is due to complete Dec 21 [2].