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Phase 2b findings suggest VEGF-C/D inhibition with 2.0 mg OPT-302 in combination with ranibizumab achieves superior vision gains compared to the current standard of care for nAMD.
A randomized controlled trial investigating OPT-302 suggests the therapy in combination with ranibizumab achieved significantly superior visual acuity gain in patients with neovascular age-related macular degeneration (nAMD) compared to standards of care.1
The phase 2b trial reported a positive dose response in participants with treatment-naive nAMD enrolled from over 100 sites across Europe, Israel, and the United States. Better anatomic and vision outcomes were indicated in the 2.0 mg OPT-302 group compared to the 0.5 mg group.
“Given the high prevalence of nAMD, and its substantial impact on vision, the prospect of improved vision outcomes could have a significant impact on a patient's quality of life,” investigators wrote.1
The first-in-class “trap” molecule is a biologic inhibitor of vascular endothelial growth factor (VEGF)-C and VEGF-D, while ranibizumab targets VEGF-A. In a phase 1 study, the VEGF C/D inhibitor reported favorable safety with no dose-limiting toxicity and a mean gain of 10.8 Early Treatment Diabetic Retinopathy Study (ETDRS) letters from baseline. The phase 2b trial, with a team led by Timothy L. Jackson, PhD, Professor of Retinal Research, King’s College London, investigated two different doses of the therapy to elaborate its efficacy and safety further.
Enrolled study participants were equal to or greater than 50 years old with nAMD and had a best-corrected visual acuity (BCVA) between 25 and 60 ETDRS letters (Snellen equivalent, 20/320 to 20/63). Randomization occurred in a 1:1:1 ratio into three study groups receiving six, 4-weekly, dual, sequential, intravitreal injections. The first group received 0.5 mg OPT-302 plus 0.5 mg ranibizumab, and the second group received 2.0 mg OPT-302 plus 0.5 mg ranibizumab, while the sham group received sham plus 0.5 mg ranibizumab.
Between December 2017 and November 2018, a total of 366 participants were randomized and 348 (95%) completed the study to Week 24. After analysis, the study met the primary endpoint, with a statistically superior gain in mean BCVA comparing the 2.0 mg OPT-302 with ranibizumab group to ranibizumab with sham (+14.2 ± 11.61 versus +10.8 ± 11.52 letters; P = .01).
The King’s College London team observed a dose response, with overall trends leaning towards better anatomic and vision outcomes in the 2.0 mg OPT-302 group. The data show the proportion of participants gaining ≥15 ETDRS BCVA letters was greatest in the 2.0 mg OPT-302 group (45.0%), followed by the sham (40.5%) and 0.5 mg (33.0%) groups. Further results from the analysis show the mean decrease in OCT CST was similar in the 0.5 mg and 2.0 mg groups, of which both were greater than the sham group.
Prespecified exploratory endpoints were additionally indicative of the primary outcome, suggesting the proportion of participants gaining ≥10 letters was more significant in the 2.0 mg OPT-302 group than in the sham group (70.0% versus 57.8%).
The study noted no safety concerns were reported with either dose of OPT-302, with study eye adverse events being similar across the three groups. Data show slightly more ocular adverse events related to the injection procedure in the 0.5 mg and 2.0 mg OPT-302 group (28.3% and 29.8%) versus sham (24.8%). Two participants died in the sham group, but neither death was considered related to the biologic product.
Investigators cited no current knowledge of another intravitreal treatment in development that has shown superiority over anti-VEGF-A therapy in nAMD, suggesting the findings’ clinical relevance to patients who experience insufficient clinical response despite receiving regular therapy.
“Notwithstanding the clinical relevance of reduced dosing, and reduced cost, many patients’ key aim is to preserve or improve their vision, and a drug that has the potential to provide the best visual outcomes would have considerable clinical utility,” they wrote.1
1. Jackson TL, Slakter J, Buyse M, Wang K, Dugel PU, Wykoff CC, Boyer DS, Gerometta M, Baldwin ME, Price CF, A randomized controlled trial of OPT-302, a VEGF-C/D inhibitor for neovascular age-related macular degeneration, Ophthalmology (2023), doi: https://doi.org/10.1016/ j.ophtha.2023.02.001.