Intravitreal Aflibercept 8 mg in Neovascular Age-related Macular Degeneration: 96-Week Results from the Randomized Phase 3 PULSAR Trial.

Abstract

Purpose: To follow up the previously published comparison of aflibercept 8 mg at extended dosing intervals versus aflibercept 2 mg every 8 weeks, in patients with neovascular age-related macular degeneration (nAMD) through 48 weeks, we now report efficacy, durability and safety analyses through 96 weeks.

Design: PULSAR (NCT04423718): phase 3, randomized, non-inferiority, 96-week trial.

Participants: Treatment-naive adults aged ≥50 years with active, subfoveal choroidal neovascularization secondary to nAMD.

Methods: Patients were randomized 1:1:1 to aflibercept 8 mg every 12 weeks (8q12), aflibercept 8 mg every 16 weeks (8q16), or aflibercept 2 mg every 8 weeks (2q8), following three initial monthly doses; dosing intervals in 8-mg groups were modified based on prespecified criteria.

Main outcome measures: Change from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT); proportion of patients maintaining or extending their randomized dosing intervals; safety outcomes.

Results: Of 1009 patients treated, 869 (8q12: n=291; 8q16: n=292; 2q8: n=286) completed treatment through Week 96. LS mean (95% CI) change from baseline in BCVA at Week 96 was +5.6 (4.1-7.1), +5.5 (4.0-7.0), and +6.6 (5.2-8.0) letters in the 8q12, 8q16, and 2q8 groups, respectively; 8q12 and 8q16 differences versus 2q8 in LS mean BCVA changes at Week 96 met the non-inferiority criteria specified for primary endpoint at Week 48. Mean (SD) change in CRT from baseline was ‒143.9 (123.6), ‒153.4 (140.8), and ‒135.8 (133.1) μm in the 8q12, 8q16 and 2q8 groups, respectively. Patients completing 96 weeks of treatment in the 8q12, 8q16 and 2q8 groups received a mean number of 9.7, 8.2, and 12.8 active injections, respectively. Of these, 87% of patients in the 8q12 group had last assigned dosing intervals of ≥12 weeks, while 78%, 53% and 31% of patients in the 8q16 group qualified for last assigned dosing intervals of ≥16 weeks, ≥20 weeks, and 24 weeks, respectively. Incidence of ocular treatment-emergent adverse events was similar across treatment groups.

Conclusion: Aflibercept 8 mg delivered sustained disease control in patients with nAMD, maintaining improvements in visual and anatomic outcomes through Week 96 with extended dosing intervals and similar safety profile to aflibercept 2 mg.