Open-label Phase 2a study of AG-73305, a novel bi-specific Fc-fusion protein for the treatment of diabetic macular edema

Abstract

Purpose : AG-73305 is a bi-specific (anti-VEGF and anti-integrin) Fc-fusion protein designed to target ligands and receptors which play a critical role in retinal diseases. This Phase 2a clinical study aims to evaluate the safety and efficacy of a single AG-73305 intravitreal injection for the treatment of diabetic macular edema (DME).

Methods : This ongoing, single-dose, dose-escalation, multi-center, open-label, 28-week study enrolled DME patients who were either previously treated or naïve to anti-VEGF therapy. Intravitreal doses of 0.5, 1, 2, and 4 mg are planned. Patients were followed for up to 6-months post-injection. The efficacy measures were change in best corrected visual acuity (BCVA) and change in central subfield thickness (CST) by optical coherence tomography (OCT) from baseline to 24 weeks. This analysis includes data up to 1 mg doses.

Results : Preliminary data on 6 patients with doses of 0.5 mg (N=3) and 1 mg (N=3) are available. There were no dose-limiting toxicities noted. AG-73305 showed an excellent safety profile, with mild anterior chamber cell and flare which resolved with topical steroid treatment. Improvements in BCVA were seen as early as Week 1 post-injection and were maintained over 3 months. Similar improvements in CST were also observed. One patient, who was a non-responder to bevacizumab, responded well to AG-73305 with BCVA improvement of 9 ETDRS letters.

Conclusions : AG-73305 showed a dose-dependent improvement in BCVA and CST following a single intravitreal dose in DME patients and has the potential to be a safe, new, long-lasting treatment.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.