According to the results of a phase 2 proof-of-concept study, treatment with aflibercept 8 mg may offer better results for patients with neovascular AMD (nAMD) than treatment with aflibercept 2 mg while maintaining similar safety-related outcomes.
Study design
This phase 2, randomized, single-masked trial enrolled patients with treatment-naïve nAMD. A total of 106 eligible patients (106 eyes) aged 50 years or older with baseline vision limited to 20/32–20/320 were randomized 1:1 to receive intravitreal injections of 8 mg or 2 mg of aflibercept (once monthly for 3 doses, and then at weeks 20 and 32). Additional treatment could be completed as needed based on prespecified retreatment criteria. Outcomes were assessed at weeks 16 and 44. The coprimary outcomes were the proportion of eyes without fluid (intraretinal or subretinal) at 16 weeks and the safety profile.
Outcomes
At week 16, 50.9% of eyes in the 8-mg group had no fluid vs only 34.0% in the 2-mg group (p = 0.08). At week 44, the proportion of eyes without fluid was 39.6% in the 8-mg group vs 28.3% in the 2-mg group (p = 0.22), with a mean change in BCVA of +7.9 vs +5.1 letters, respectively (p = 0.20). No safety differences were noted between arms. Over the 44-week study period, participants in both groups received a mean of 5.8 injections.
Limitations
This was a proof-of-concept study, with a limited sample size and study duration. Notably, the 2-mg arm was not dosed per current label treatment intervals, potentially underestimating treatment efficacy.
Clinical significance
While no significant differences between arms were noted in the primary outcomes of this study, trends suggested greater therapeutic benefit associated with the 8-mg dose, with a larger proportion of fluid-free eyes and improved visual acuity seen in this cohort than among patients who received 2 mg. These results support the recent FDA approval of aflibercept 8 mg for the treatment of neovascular AMD and diabetic macular edema with dosing every 8–16 weeks after three initial monthly treatments. Results of the ongoing phase 3, 96-week PULSAR study evaluating the efficacy of aflibercept 8 mg vs on-label dosing of aflibercept 2 mg in neovascular AMD will provide further details regarding long-term anatomic and visual acuity outcomes of aflibercept 8 mg at extended treatment intervals.
Financial disclosures: Dr. M. Ali Khan discloses financial relationships with Allergan, Apellis Pharmaceuticals, Genentech (Consultant/Advisor); Regeneron Pharmaceuticals (Grant Support).