Efficacy and Safety of OPT-302 in combination with Ranibizumab for Polypoidal Choroidal Vasculopathy

Abstract

Purpose : Vascular endothelial growth factor-C and D (VEGF-C/-D) are angiogenic mediators which may contribute to treatment escape with VEGF-A suppression of retinal disease. The aim of this investigation was to assess combination therapy of OPT-302 (anti-VEGF-C/-D) with ranibizumab (anti-VEGF-A) for the treatment of polypoidal choroidal vasculopathy (PCV).

Methods : Prespecified subgroup analysis of a Phase 2b, randomized, sham-controlled study of OPT-302 administered to treat neovascular age-related macular degeneration (NCT03345082). Participants in the subgroup analysis had PCV identified in the study eye by masked readers at a central reading center. Polyps were identified and defined using multimodal imaging, including fundus photography (subretinal orange nodules), fluorescein angiography (typical primarily occult multifocal lesions) and spectral domain optical coherence tomography (notched, sharply peaked or multi-lobular pigment epithelial detachments with or without a ring of hyperreflectivity along the inner border). Eyes were randomized to receive 6-monthly intravitreal injections of either ranibizumab (0.5 mg) + OPT-302 (0.5 mg or 2 mg) or ranibizumab + sham. Outcomes measures included best-corrected Early Treatment Diabetic Retinopathy Study visual acuity (BCVA), anatomic changes, and safety / tolerability.

Results : Sixty-six participants with PCV were included. OPT-302 with ranibizumab was well tolerated, consistent with the full study population, with no clinically significant safety findings. The mean BCVA change from baseline to week 24 showed a dose response in participants with PCV, who gained 13.5 letters in the 2 mg OPT-302 combination group (n = 22), 10.9 letters in the 0.5 mg OPT-302 combination group (n = 24) and 6.9 letters in the ranibizumab control group (n = 20). The +6.7 letters comparative superiority of 2 mg OPT-302 combination therapy over ranibizumab (p = 0.0253) was accompanied by a greater proportion of participants gaining ≥ 10 or ≥ 15 letters, fewer losing ≥ 5 letters and fewer with retinal fluid at week 24.

Conclusions : OPT-302 combination therapy was well tolerated, with greater improvements in BCVA and less retinal fluid compared to ranibizumab monotherapy in participants with symptomatic macular PCV. Larger studies of dual inhibition of VEGF-C/-D and VEGF-A for the treatment of PCV are warranted.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.