David Xu, MD
Vitreoretinal Surgery
Wills Eye Hospital
Dr. David Brown presented the one-year results of the phase 2, randomized, single-masked study of high dose aflibercept for neovascular age-related macular degeneration (AMD) in the CANDELA study. Building upon prior evaluation with ranibizumab 2.0 mg, the study evaluates whether high dose anti-VEGF can offer benefits to neovascular AMD patients such as reducing the number of “incomplete responders,” yielding better anatomic/visual outcomes, or potentially reducing treatment burden. In the SAVE (super-dose anti-VEGF) trial of ranibizumab, the higher 2.0 mg ranibizumab dose achieved better visual and anatomic gains in recalcitrant neovascular AMD on the monthly treatment arm.
As for aflibercept, studies show that ~50% of wet AMD of patients can be effectively treated with q 12 quarterly dosing. The CANDELA trial evaluated whether high dose aflibercept 8 mg injection could maintain anatomic/functional outcomes at longer dosing intervals as compared to standard aflibercept. The study enrolled 106 naïve wet AMD patients over an approximately one year study duration. At week 44, there was a greater number of patients without macular fluid in the high dose aflibercept arm, and a trend towards more patients without fluid in the center subfield as well as anywhere in the macula at week 16. Visual function was well maintained in both groups, although the number of patients with ≥5-letter, ≥10-letter, and ≥15-letter loss were lower in the high-dose group. No new safety signals were identified in the study, and overall high dose aflibercept appears to have a similar safety profile as the standard dose.
Two large-scale phase 3 studies are underway to compare high dose vs standard dose aflibercept for neovascular AMD (PULSAR, NCT04423718) and diabetic macular edema (PHOTON, NCT04429503).
