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  • OPT-302: A VEGF C/D Inhibitor for Wet AMD

    By Lynda Seminara
    Selected by Russell N. Van Gelder, MD, PhD
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    Journal Highlights

    Ophthalmology, June 2023

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    Neovascular age-related macular de­generation (nAMD) is driven by VEGF A, C, and D, all of which promote angiogenesis and vascular permeabil­ity. The standard of care for nAMD is intravitreal injection of anti-VEGF A drugs, but this treatment does not affect the VEGF C or D pathway. This may explain why the response to traditional therapy is incomplete in many cases. Jackson et al. studied the efficacy and safety of OPT-302, a biologic inhibitor of VEGF C and D, given intravitreally in combination with ranibizumab. They also compared the dual-treatment strategy with ranibizumab monother­apy and found that the combination achieved superior VA gains.

    This phase 2b, double-masked trial included patients with treatment-naïve nAMD who were enrolled among 109 sites. They were assigned randomly to one of three groups: ranibizumab alone (sham control), ranibizumab + 0.5 mg OPT-302, or ranibizumab + 2.0 mg OPT-302. The ranibizumab dose was the same (0.5 mg) for all study arms. Each participant received six injections, at four-week intervals. The main out­come was the mean change in BCVA from baseline to week 24, according to criteria of the Early Treatment Diabetic Retinopathy Study (ETDRS). Other outcomes were changes from baseline to week 24 in the proportion of patients who gained or lost ≥15 ETDRS BCVA letters; area under the ETDRS BCVA curve over time; and change in central subfield thickness (CST), intraretinal fluid, and subretinal fluid observed by SD-OCT.

    Overall, 366 participants were recruited from December 2017 through November 2018: 122 received combi­nation treatment with 0.5 mg OPT-302, 123 received combination treatment with 2.0 mg OPT-302, and 121 were given ranibizumab only. The mean (±SD) VA gain with 2.0 mg OPT-302 was significantly better than with ran­ibizumab alone (+14.2 ± 11.61 letters vs. +10.8 ± 11.52 letters; p = .01). Visual outcomes did not differ significantly between the 0.5-mg OPT-302 and ranibizumab-only groups. Secondary BCVA outcomes were superior with 2.0 mg OPT-302. Compared with ra­nibizumab treatment alone, structural outcomes were better with either dose of OPT-302. The incidence and type of adverse events were similar in all study arms. A serious adverse event occurred in 16, seven, and 10 recipients of 0.5 mg OPT-302, 2.0 mg OPT-302, and ranibizumab monotherapy, respective­ly. There were two deaths (both in the ranibizumab-only group); neither was deemed related to the study treatment.

    The potential to enhance visual out­comes for patients with nAMD could translate to meaningful improvement in their quality of life, said the authors. They acknowledged that longer studies are needed to determine whether the visual benefits are sustained and to ex­plore the long-term safety of OPT-302.

    The original article can be found here.