Results of a phase 1b study support the potential of sozinibercept (OPT-302; Opthea Ltd), a VEGF-C and VEGF-D “trap” protein, in combination with aflibercept (Eylea; Regeneron) for patients with center-involved diabetic macular edema (DME). The study findings were published in the December issue of Translational Vision Science & Technology, the official journal of the Association for Research in Vision and Ophthalmology (ARVO).

The open-label, multicenter trial (NCT03397264) evaluated the safety, pharmacokinetics, and efficacy of escalating doses of sozinibercept (0.3, 1, or 2 mg) in combination with aflibercept (2 mg) in 9 patients with persistent DME after an average of 6.3 prior anti–VEGF-A treatments. The study’s primary endpoint was safety, while secondary endpoints included changes in best-corrected visual acuity (BCVA) and central subfield thickness (CST).

Sozinibercept combination therapy demonstrated a favorable safety profile with no dose-limiting toxicities, the researchers found. At week 12, patients showed a mean BCVA improvement of +7.7 ETDRS letters from baseline (65 letters). CST decreased by -71 µm from a baseline of 434 µm, with 67% of patients achieving at least a 50% reduction in excess foveal thickness. Higher doses of sozinibercept were associated with greater improvements in both BCVA and CST.

By targeting VEGF-C and VEGF-D, sozinibercept may neutralize alternative pathways involved in angiogenesis and vascular permeability, which are implicated in DME pathophysiology, the study authors reported. Combination therapy with sozinibercept and aflibercept not only improved visual and anatomic outcomes but also demonstrated the potential to overcome resistance mechanisms observed with VEGF-A inhibitors. These findings pave the way for larger randomized trials to further evaluate the therapeutic potential of sozinibercept for DME.

OPT-302 is currently being studied as a treatment for neovascular (“wet”) age-related macular degeneration in a pair of phase 3 trials, ShORe (in combination with ranibizumab [Lucentis; Genentech]) and COAST (in combination with Eylea).