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Purpose: To evaluate the efficacy and safety of aflibercept 8 mg versus 2 mg in patients with treatment-naïve macular edema following retinal vein occlusion (MEfRVO).

Methods: QUASAR (NCT05850520) was a 64-week, randomized, double-masked, active-controlled, noninferiority, Phase 3 trial of patients aged ≥18 years with MEfRVO, enrolled in 27 countries across Europe, America, Japan, and the Asia Pacific region. Patients were assigned 1:1:1 to aflibercept 8 mg every 8 weeks (wks), after 3 (8q8/3 [n=293]) or 5 (8q8/5 [n=298]) initial monthly doses, or aflibercept 2 mg every 4 wks (2q4 [n=301]). Patients who met prespecified criteria could have their dosing intervals shortened if their last dosing interval was >4 weeks, or extended by 4 weeks starting at Week 32 for 8q8/3 and 2q4 and at Week 40 for 8q8/5. The minimum dosing interval was every 4 weeks (Q4). The primary endpoint was best-corrected visual acuity (BCVA) change from baseline (BL) to Week 36. Key secondary endpoint was number of injections from BL to Week 64.

Results: Aflibercept 8 mg showed robust and non-inferior BCVA gains versus 2 mg, with least squares (LS) mean difference (2-sided 95% CI) in BCVA versus 2q4 at W36 of -0.1 (-2.0, 1.9) letters for 8q8/3 and +0.8 (-1.1, 2.7) letters for 8q8/5 (both p<0.0001, 4-letter non-inferiority margin). At Week 64, up to 3 fewer injections of aflibercept 8 mg versus 2 mg were administered, the LS mean difference (2-sided 95% CI) in number of injections versus 2q4 was -3.2 (-3.5, -3.0) and -2.2 (-2.4, -2.0) for 8q8/3 and 8q8/5, respectively. At Week 64, 81.4% (8q8/3) and 78.5% (8q8/5) versus 67.8% (2q4) had a last completed dosing interval of ≥Q12; and 40.5% of the 8q8/3 group were assigned to Q20 intervals. Nearly 3-fold fewer patients were assigned a Q4 dosing interval with 8q8/3 and 8q8/5 versus 2q4 at W64 (4.8% & 3.5% vs 13.0%). The aflibercept 8 mg safety profile was consistent with the established safety profile of aflibercept 2 mg in patients with MEfRVO. Representative case studies will be presented to substantiate the reported findings.

Conclusions: In patients with MEfRVO, aflibercept 8 mg met the primary and key secondary endpoints demonstrating non-inferiority in BCVA gains at Week 36, which were maintained through Week 64 with up to 3 fewer injections compared with aflibercept 2 mg. More patients treated with aflibercept 8 mg achieved every 12 weeks or greater dosing intervals, fewer required monthly intervals, and up to 41% of the 8q8/3 group qualified for every 5 month intervals. Overall, aflibercept 8 mg provided robust visual outcomes with fewer injections, and with a comparable safety profile to aflibercept 2 mg.