A Randomized Controlled Trial of OPT-302, a VEGF-C/D Inhibitor for Neovascular Age-Related Macular Degeneration

Purpose: Neovascular (wet) age-related macular degeneration (nAMD) is driven by VEGFs A, C, and D, which promote angiogenesis and vascular permeability. Intravitreal injections of anti-VEGF-A drugs are the standard of care, but these do not inhibit VEGF-C and D, which may explain why many patients fail to respond fully. This trial aimed to test the safety and efficacy of OPT-302, a biologic inhibitor of VEGF-C and D, in combination with the anti-VEGF-A inhibitor ranibizumab. Participants: Participants with treatment-naive nAMD were enrolled from 109 sites across Europe, Israel, Methods: Participants were randomized to 6, 4-weekly, intravitreal injections of 0.5 mg OPT-302, 2.0 mg OPT-302, or sham, plus intravitreal 0.5 mg ranibizumab. Main Outcome Measures: The primary outcome was mean change in ETDRS best-corrected visual acuity (BCVA) at 24 weeks. Secondary outcomes (comparing baseline with week 24) were the proportion of participants gaining or losing >= 15 ETDRS BCVA letters; area under the ETDRS BCVA over time curve; change in spectraldomain OCT (SD-OCT) central subfield thickness; and change in intraretinal fluid and subretinal fluid on SD-OCT. Results: Of 366 participants recruited from December 1, 2017, to November 30, 2018, 122, 123, and 121 were randomized to 0.5 mg OPT-302, 2.0 mg OPT-302, and sham, respectively. Mean (+/- standard deviation) visual acuity gain in the 2.0 mg OPT-302 group was significantly superior to sham (+14.2 +/- 11.61 vs. +10.8 +/- 11.52 letters; P = 0.01). The 0.5 mg OPT-302 group was not significantly different than the sham group (+9.44 +/- 11.32 letters; P = 0.83). Compared with sham, the secondary BCVA outcomes favored the 2.0 mg OPT-302 group, with structural outcomes favoring both OPT-302 dosage groups. Adverse events (AEs) were similar across groups, with 16 (13.3%), 7 (5.6%), and 10 (8.3%) participants in the lower-dose, higher-dose, and sham groups, respectively, developing at least 1 serious AE. Two unrelated deaths both occurred in the sham arm. Conclusions: Significantly superior vision gain was observed with OPT-302 2.0 mg combination therapy, versus standard of care, with favorable safety (ClinicalTrials.gov identifier: NCT03345082). Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2023;130:588-597 (c) 2023 by the American Academy of Ophthalmology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Automated summary

This study tested the efficacy and safety of OPT-302 in combination with ranibizumab for the treatment of wet age-related macular degeneration. The results showed that the combination therapy with OPT-302 2.0 mg significantly improved visual acuity compared to the standard of care, with favorable safety.