Clinical proof of concept for anti-FGF2 therapy in exudative age-related macular degeneration: phase 1 and phase 2 trials in treatment-naïve and anti-VEGF pretreated patients

Abstract Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are the first-line treatment for exudative/wet age-related macular degeneration (wet AMD). Alternative mechanisms of action may be helpful for treatment of this very common disease. Here we investigated an anti-fibroblast growth factor-2 (FGF2) aptamer, RBM-007, a next generation therapeutic for the treatment of wet AMD. First, a phase 1 (SUSHI) study confirmed the safety, tolerability and bioactivity of a single intravitreal injection of RBM-007. Second, a phase 2 (TOFU) study did not show any improvement in patients, who had previously undergone anti-VEGF treatment, however it did prevent disease progression. Third, in a phase 2 (TEMPURA) study patients treated with RBM-007, who had not received any prior anti-VEGF treatment, showed improvement and no further macular degeneration, with striking improvement of visual acuity and central subfield thickness in some of the patients. These results demonstrate clinical proof of concept for aptamer based anti-FGF2 therapy of wet AMD.