Intravitreal aflibercept 8 mg in patients with polypoidal choroidal vasculopathy (PCV): A Phase 3 PULSAR trial subgroup analysis

Abstract

Purpose : PULSAR (NCT04423718) is an ongoing, double-masked, 96-week, Phase 3 trial in patients aged ≥50 years with treatment-naïve neovascular age-related macular degeneration randomly assigned 1:1:1 to intravitreal aflibercept 8 mg every 12 or 16 weeks (8q12, 8q16) or 2 mg every 8 weeks (2q8), each after three initial monthly injections. Efficacy in patients with PCV was assessed in prespecified and post hoc analyses.

Methods : The primary endpoint was change from baseline (BL) in best-corrected visual acuity (BCVA) at Week 48. The key secondary endpoint was the proportion of patients with no intraretinal/subretinal fluid (IRF/SRF) in central subfield at Week 16. PCV was confirmed by the central reading center: indocyanine green angiography (ICGA) was optional and undertaken in 297 patients, mainly in Asian countries. Subgroup analyses were descriptive only and values presented without imputation.

Results : Overall, 1,009 patients were randomly assigned and treated, and the primary endpoint was met with aflibercept 8q12 and 8q16 vs 2q8 (non-inferiority margin at 4 letters), with observed mean±SD BCVA changes from BL of 6.7±12.6 (8q12), 6.2±11.7 (8q16), and 7.6±12.2 (2q8) letters (BL: 59.9±13.4, 60.0±12.4, and 58.9±14.0, respectively). Among 297 patients who underwent ICGA, PCV was present in 141 (2q8: n=54; 8q12: n=45; 8q16: n=42) and absent in 153 (n=3 missing). In patients with PCV, observed mean±SD change from BL in BCVA at Week 48 was similar with 8q12, 8q16, and 2q8: 9.3±13.2, 8.5±7.8, and 9.5±11.7 letters, respectively (BL: 56.7±13.4, 60.1±11.3, and 57.6±15.4, respectively). In the PCV subgroup, 67.8% of patients in the pooled 8 mg groups had no central subfield IRF/SRF at Week 16 versus 63.0% in the 2q8 group. In those who completed the Week 48 visit, 33/42 (78.6%) in the 8q12 group maintained 12-week treatment intervals, and 33/38 (86.8%) in the 8q16 group maintained 16-week intervals; overall, 69/80 (86.3%) of patients with PCV receiving 8 mg were maintained on ≥12-week treatment intervals. The safety profile of aflibercept was similar in patients with PCV and the overall PULSAR nAMD population.

Conclusions : In patients with PCV, aflibercept 8 mg provides similar improvements in BCVA and fluid resolution at Week 48 as compared to aflibercept 2 mg every 8 weeks, with >85% of patients on aflibercept 8 mg maintaining extended injection intervals of 12 or 16 weeks.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.