Compared with 2 mg, aflibercept 8 mg administered at varying intervals was more effective, with comparable safety, according to results from PULSAR.
The phase 3 PULSAR trial of aflibercept 8 mg met its primary endpoint—best-corrected visual acuity (BCVA) change at 48 weeks—among patients with treatment-naïve neovascular age-related macular degeneration (nAMD).
Jignesh I. Patel, MD, presented the findings from PULSAR at the American Society of Retina Specialists 2023 Annual Meeting. The trial aimed “to determine the therapeutic benefit, injection interval, and safety of aflibercept 8 mg versus 2 mg,” according to Dr. Patel and colleagues.
The ongoing 96-week trial included patients aged 50 and older with nAMD. The researchers randomly assigned patients 1:1:1 to receive aflibercept 8 mg every 12 weeks (8q12) or 16 weeks (8q16) or aflibercept 2 mg every 8 weeks (2q8). The primary endpoint was the change in BCVA from baseline at week 48, with a noninferiority margin at four letters. The key secondary endpoint was the proportion of patients with no intraretinal/subretinal fluid (IRF/SRF) in the central subfield at week 16; other secondary endpoints included safety.
Extended Dosing Sustainable, With Comparable Safety Profile
The 48-week findings presented by Dr. Patel included 1,009 patients (8q12: n=335; 8q16: n=338; 2q8: n=336). The mean age was 74.5, and 54.5% of patients were women.
Results showed that the primary endpoint was met with aflibercept 8 mg (8q12 vs 2q8: P=0.0009; 8q16 vs 2q8: P=0.0011). The mean change from baseline in BCVA at week 48 was +6.7 with aflibercept 8q12, +6.2 with 8q16, and +7.6 with 2q8.
The 12-week treatment intervals were sustained by 79% of patients in the 8q12 group; a comparable percentage (77%) in the 8q16 group sustained the 16-week treatment intervals in year 1. Altogether, 83% of patients treated with aflibercept 8 mg sustained the treatment interval of 12 or more weeks in year 1.
The 8 mg dose demonstrated superior drying ability versus the 2 mg dose at week 16, with no IRF/SRF in the central subfield seen in 63% of patients in the 8-mg arm versus 52% of patients in the 2-mg arm (P=0.0002). Additionally, the safety of aflibercept 8 mg was comparable to the safety profile for aflibercept 2 mg.
Dr. Patel and colleagues noted that “the vast majority” of patients continued with extended dosing of 12 weeks or more (83% in both 8-mg arms) and 16-week dosing (77% in 8q16).
“Overall, aflibercept 8 mg provides greater therapeutic benefit, an extended injection interval, and equivalent safety versus aflibercept 2 mg,” the researchers wrote.
