Aflibercept 8 mg monotherapy shows maintained efficacy over 96 weeks, with the ability to extend dosing intervals beyond every 16 weeks, in patients with PCV in the PULSAR Phase 3 trial

Abstract

Purpose : To evaluate the efficacy and safety of aflibercept 8 mg monotherapy in patients with treatment-naïve polypoidal choroidal vasculopathy (PCV) over 96 weeks.

Methods : PULSAR (NCT04423718) is a double-masked, 96-week, Phase 3 trial in patients aged ≥50 years with treatment-naïve neovascular age-related macular degeneration (nAMD). Patients were randomly assigned 1:1:1 to receive intravitreal aflibercept 8 mg every 12 or 16 weeks (8q12 or 8q16) or 2 mg every 8 weeks (2q8), each after three initial monthly injections. The dosing regimens in the 8q12 and 8q16 groups could be shortened from Week 16 and extended from Week 52 based on predefined protocol criteria. This subgroup analysis focused on patients with PCV as confirmed by indocyanine green angiography (ICGA) at a central reading center. Subgroup analyses were exploratory only.

Results : In PULSAR, PCV was present in 139 of the 296 patients with ICGA results (2q8: n=54; 8q12: n=44; 8q16: n=41). All three treatment groups showed similar visual acuity gains over 96 weeks, with a last observation carried forward (LOCF) mean±SD best-corrected visual acuity (BCVA) gain from baseline (BL) at Week 96 of 8.4±12.8, 8.2±9.0, and 9.6±12.1 letters for 8q12, 8q16, and 2q8 (BL: 56.3±13.3, 60.1±11.5, and 57.6±15.5 letters), respectively. In the overall PULSAR population, these gains were 5.5±14.9, 5.4±13.3, and 7.1±13.0 letters (BL: 59.9±13.4, 60.0±12.4, and 58.9±14.0 letters), respectively. In patients with PCV who completed the Week 96 visit, 77.5% in the 8q12 arm had maintained ≥12 week dosing intervals, and 77.8% in the 8q16 arm had maintained ≥16−week dosing intervals. At Week 96, in patients receiving aflibercept 8 mg, the dosing interval could be extended to ≥20 weeks and 24 weeks in 56.6% and 34.2% patients, respectively. Aflibercept 8 mg markedly reduced the area of polypoidal lesions from screening to Week 96 (0.15 mm² vs. 0.07 mm²). The safety profile of aflibercept 8 mg and 2 mg was similar in the PCV subgroup and overall PULSAR population.

Conclusions : Aflibercept 8 mg (8q12 and 8q16) provided similar improvements in BCVA in patients with PCV compared with aflibercept 2 mg given every 8 weeks. Overall, aflibercept 8 mg monotherapy showed BCVA gains that were largely maintained over 96 weeks with the ability to extend treatment intervals in patients with PCV.

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