Abstract
Purpose :
Systemic tumor necrosis factor-alpha (TNF-α) therapy is effective for the treatment of immune-mediated diseases including non-infectious uveitis (NIU). The benefit of local anti-TNF-α therapy in patients remains unclear. Eyevensys is developing non-viral gene therapies utilizing a proprietary electrotransfection system to deliver plasmids to the ciliary muscle allowing sustained therapeutic protein expression in the eye. EYS606 encodes a recombinant fusion anti-TNF-α protein linking the soluble TNF-α p55 receptor 1 to the human IgG1 Fc domain. We present preliminary findings from an ongoing first-in-human study investigating the safety and tolerability of EYS606 in patients with NIU.
Methods :
EYS606-CT1 is a two-part, 24-week multicenter, open-label, phase I/II study investigating the safety and tolerability EYS606. In Part 1 of the study, end stage NIU patients are assigned to treatment with escalating EYS606 doses while in Part 2, patients with less severe, active NIU will receive the maximally tolerated EYS606 dose. The primary endpoint is adverse events with longer term safety and clinical activity assessed as secondary endpoints. EYS606 biodistribution in the urine, plasma, saliva and aqueous humor is analyzed as an assessment of safety and as a potential efficacy biomarker.
Results :
To date, 7 of 9 planned patients have been treated in Part 1 of the study with one of the three escalating EYS606 doses. The majority of reported adverse events following EYS606 treatment have been ocular, mild to moderate in severity and related to the administration procedure. One reported serious adverse event, cellulitis, was neither related to the study drug or the administration procedure. One patient treated with the lowest EYS606 dose in cohort 1 experienced at least a 10 letter improvement in ETDRS visual acuity within 2 weeks following the treatment administration. An update of the Part 1 study results including enrollment, demographics, preliminary safety and efficacy results will be presented.
Conclusions :
EYS606 is the first gene therapy approach for the treatment of NIU inducing sustained intraocular expression of a potent TNF-α inhibitor. The EYS606-CT1 study will further clarify potential benefits, risks, and clinical effects of sustained therapeutic protein expression in the eye resulting from treatment with EYS606.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.