Aflibercept 8 mg Sustains 96-Week Outcomes in PULSAR nAMD Trial

Key Takeaways

• Week 96 visual and anatomic outcomes were maintained, and BCVA differences versus 2q8 met the noninferiority criteria specified for the primary end point at week 48.
• Extended intervals were common with aflibercept 8 mg among patients completing 96 weeks of treatment, with lower mean active injection counts and many patients remaining at 12 weeks or longer.
• Ocular treatment-emergent adverse events were similar across the three assigned regimens.

At 96 weeks, aflibercept 8 mg maintained visual and anatomic outcomes in treatment-naive neovascular age-related macular degeneration, with patients completing treatment averaging 9.7 or 8.2 active injections versus 12.8 with aflibercept 2 mg every 8 weeks. The comparison comes from PULSAR, a randomized phase 3 noninferiority study in adults aged 50 years or older. The 96-week analysis compared extended-interval dosing in the 8 mg groups with a fixed every-8-week 2 mg regimen. Visual and anatomic outcomes were maintained alongside longer dosing intervals and similar ocular safety through follow-up.

The PULSAR phase 3 trial randomized treatment-naive adults aged 50 years or older with neovascular age-related macular degeneration in a 1:1:1 ratio. After 3 initial monthly doses, participants received aflibercept 8 mg every 12 weeks, aflibercept 8 mg every 16 weeks, or aflibercept 2 mg every 8 weeks. Dosing intervals in the 8 mg groups could be modified using prespecified criteria during follow-up. Main outcome measures included change from baseline in BCVA and central retinal thickness, interval maintenance or extension, and safety outcomes. By week 96, the comparison centered on maintained efficacy, interval durability, and ocular safety across the assigned regimens.

Least-squares mean BCVA change from baseline at week 96 was +5.6 letters for 8q12, +5.5 for 8q16, and +6.6 for 2q8. The corresponding 95% confidence intervals were 4.1 to 7.1, 4.0 to 7.0, and 5.2 to 8.0 letters. BCVA differences versus 2q8 met the noninferiority criteria specified for the primary end point at week 48. Central retinal thickness also decreased in all three groups at week 96. Mean central retinal thickness changes from baseline were -143.9 μm, -153.4 μm, and -135.8 μm across groups. Visual and anatomic outcomes were maintained across groups through week 96.

Mean active injections over 96 weeks were 9.7 for 8q12, 8.2 for 8q16, and 12.8 for 2q8 among patients who completed the full 96 weeks of assigned treatment follow-up. Among these patients, 87% in 8q12 had last assigned dosing intervals of at least 12 weeks. In 8q16, 78% qualified for at least 16 weeks, 53% for at least 20 weeks, and 31% for 24 weeks. Among 1009 treated patients, 869 completed treatment through week 96, and many assigned to aflibercept 8 mg remained on extended intervals.

Ocular treatment-emergent adverse events were similar across groups over the 96-week follow-up. The authors framed the 96-week results as sustained disease control relative to the 2 mg every-8-week comparator. Investigators concluded that aflibercept 8 mg maintained visual and anatomic improvements through week 96 while supporting extended dosing intervals. That overall pattern was accompanied by a safety profile similar to aflibercept 2 mg.