Abstract
Purpose:
To assess the safety and efficacy of Fovista™ in combination with ranibizumab compared to ranibizumab monotherapy in a large (449 patients) randomized Phase 2b trial in neovascular AMD patients.
Methods:
449 patients with neovascular AMD were randomized in a prospective, controlled, superiority trial to receive one of the following treatment regimens administered every 4 weeks for 24 weeks: Fovista™ 0.3 mg in combination with ranibizumab 0.5 mg; Fovista™ 1.5 mg in combination with ranibizumab 0.5 mg; or sham in combination with ranibizumab 0.5 mg.
Results:
The combination of Fovista™ (1.5 mg) with ranibizumab met the pre-specified primary endpoint of superiority in mean visual acuity gain compared to ranibizumab monotherapy (10.6 ETDRS letters at week 24, compared to 6.5 letters, p=0.019). An additional 62% benefit from baseline was noted in the Fovista™ (1.5 mg) combination therapy arm over ranibizumab monotherapy. A classic dose-response curve was observed. Enhanced visual outcomes for Fovista™ 1.5 mg combination therapy compared to ranibizumab monotherapy were present at every monthly timepoint. The relative magnitude of visual benefit increased over time. The superiority of Fovista™ 1.5 mg combination therapy over ranibizumab monotherapy was consistent across all subgroups including those analyzing baseline vision, lesion size, and central retinal thickness. Fovista™ 1.5 mg combination was superior to ranibizumab monotherapy across multiple treatment endpoints including 3, 4 and 5 lines of vision gain (ETDRS chart). OCT and fluorescein angiography analysis showed patients receiving Fovista™ 1.5 mg combination therapy had greater reduction in neovascular size compared to those receiving ranibizumab monotherapy. No significant safety issues were observed for either treatment group in the trial.
Conclusions:
The combination of Fovista™ 1.5 mg and ranibizumab demonstrated alpha protected, statistical superiority in terms of mean vision gain when compared to ranibizumab monotherapy in this large controlled phase 2b trial of eyes with neovascular AMD. The increasing divergence of efficacy curves over time implies a benefit to continued anti-PDGF combination therapy. Combination therapy was well tolerated.
Keywords: 412 age-related macular degeneration •
748 vascular endothelial growth factor •
453 choroid: neovascularization