Pooled safety analysis of the CANDELA, PHOTON, and PULSAR trials up to 96 weeks demonstrates comparable safety profiles with aflibercept 8 mg and 2 mg

Abstract

Purpose : To compare the safety of aflibercept 8 mg and 2 mg in the CANDELA, PHOTON, and PULSAR trials.

Methods : CANDELA was a single-masked, open-label, 44-week, phase 2 trial: treatment-naïve patients with neovascular age-related macular degeneration (nAMD) were randomized 1:1 to receive 3 monthly doses of aflibercept 8 mg or 2 mg followed by doses at Weeks 20 and 32. PHOTON was a double-masked, 96-week, non-inferiority, phase 2/3 trial: patients with diabetic macular edema were randomized 1:2:1 to receive aflibercept 2 mg every 8 weeks after 5 monthly doses or 8 mg every 12 or 16 weeks after 3 monthly doses. PULSAR was a double-masked, 96-week, non-inferiority, phase 3 trial: patients with nAMD were randomized 1:1:1 to receive aflibercept 2 mg every 8 weeks, or 8 mg every 12 or 16 weeks after 3 monthly doses. Safety data for PHOTON and PULSAR were pooled up to Week 96 and CANDELA through Week 44.

Results : Overall, 1773 patients (aflibercept 8 mg: n=1217; aflibercept 2 mg: n=556) were treated and evaluated. Ocular treatment-emergent adverse events (TEAEs) in the study eye were reported in 47.9% and 47.3% of patients who received aflibercept 8 mg and 2 mg. The most common ocular TEAEs with aflibercept 8 mg and 2 mg were cataract (8.2% and 5.0%), reduced visual acuity (4.4% and 5.4%), vitreous floaters (4.0% and 4.0%), conjunctival hemorrhage (3.8% and 3.1%), and retinal hemorrhage (3.6% and 4.0%). Ocular hypertension was reported in 1.0% and 0.5% of patients and increased intraocular pressure (IOP) in 2.8% and 3.1% of patients with aflibercept 8 mg and 2 mg. Intraocular inflammation was reported in 1.3% and 1.6% of patients with aflibercept 8 mg and 2 mg. There were no cases of occlusive retinal vasculitis reported in the trials. Serious ocular TEAEs were reported in 2.3% and 1.3% of patients with aflibercept 8 mg and 2 mg. Serious ocular TEAEs occurring in >1 patient in either treatment group were retinal detachment (7 patients), cataract (6 patients), retinal hemorrhage (5 patients), increased IOP (3 patients), vitreous hemorrhage (3 patients), and retinal tear (2 patients). Adjudicated APTC events were reported in 3.7% and 4.1% of patients with aflibercept 8 mg and 2 mg.

Conclusions : Aflibercept 8 mg demonstrated comparable safety to 2 mg up to 96 weeks across the CANDELA, PHOTON, and PULSAR trials.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.