Abstract
Purpose :
AG-73305, a humanized Fc-fusion protein able to block VEGF and integrin pathways, was designed to target the multiple mechanisms involved in diabetic macular edema (DME). This study evaluated the safety, tolerability, systemic pharmacokinetic (PK) and immunogenicity profile of ascending doses of AG-73305 administered by intravitreal (IVT) injection in patients with DME.
Methods :
This is a multi-centered, open-labeled, single ascending dose cohort study with a sentinel patient at each dose level. The study enrolled DME patients who were either previously treated or naïve to anti-VEGF therapy. Cohort management was overseen by a Safety Review Committee (SRC) based on the acceptable safety profile, incidence and severity of adverse events, and at least one visit demonstrated clinical beneficial effect after the injection. Single intravitreal doses of 0.5, 1, 2, and 4 mg were evaluated. Patients were followed up to 6-months post-injection or 1-month after receiving rescue therapy. The efficacy measures included best corrected visual acuity (BCVA), and central subfield thickness (CST) by optical coherence tomography (OCT), and time to rescue medication.
Results :
Twenty-five (25) pateints were enrolled and completed the study. The results showed that AG-73305 was safe and well-tolerated at all doses with no vitritis, retinitis, occlusive vasculitis, nor dose-limiting toxicities noted. There were mild to moderate anterior chamber cells and flare reported which resolved with topical steroid treatment. AG-73305 provided statistically significant increases in visual acuity and anatomical improvements after a single dose compared to baseline. Data combining all 25 pateints showed mean improvement in BCVA of +6.4 ETDRS letters with mean CST reduction of -100 microns at 4 weeks post-injection. By the end of study at Week 24, more than 50% of patients did not require rescue therapy. Improvements in BCVA were seen as early as Week 1 post-injection and were maintained over 3-6 months. Similar improvements in CST were also observed.
Conclusions :
The results show that AG-73305 is safe and well-tolerated. A single intravitreal dose of AG-73305, with a novel bi-functional mechanism of action, showed improvement of BCVA and CST reduction lasting up to 24 weeks in DME patients; beyond what is expected from an anti-VEGF monotherapy.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.