Abstract
Purpose :
To evaluate the efficacy and safety of aflibercept 8 mg vs 2 mg in patients with diabetic macular edema (DME).
Methods :
PHOTON (NCT04429503) is an ongoing, double-masked, 96-week, non-inferiority trial that randomized patients with DME to receive aflibercept 8 mg every 12 or 16 weeks after 3 monthly doses (8q12 [n=328] or 8q16 [n=163]) or aflibercept 2 mg every 8 weeks after 5 monthly doses (2q8; n=167). During Weeks 16-48, patients in the 8q12 or 8q16 arms received aflibercept 8 mg in shorter intervals if they met prespecified dose regimen modification criteria denoting disease activity. The primary endpoint was the mean change from baseline in BCVA at Week 48 (non-inferiority margin at 4 letters); the key secondary endpoint was the proportion of patients with ≥2-step improvement in DRSS score at Week 48 (non-inferiority margin at 15%). The mean change from baseline in total fluorescein leakage area at Week 48 per reading center was evaluated as an exploratory endpoint.
Results :
Mean BCVA change from baseline at Week 48 was +9.2, +8.8, and +7.9 letters with 2q8, 8q12, and 8q16, respectively (least squares mean difference: non-inferiority P<0.0001 for 8q12 vs 2q8 [95% CI: -2.26, 1.13]; non-inferiority P=0.0031 for 8q16 vs 2q8 [95% CI: -3.27, 0.39]). The proportion of patients with ≥2-step improvement from baseline in DRSS score was 27%, 29%, and 20% with 2q8, 8q12, and 8q16, respectively (8q12 group met the non-inferiority margin of 15% [95% CI vs 2q8: -6.61, 10.57] whereas the 8q16 group did not [95% CI vs 2q8: -16.88, 1.84]). Through Week 48, 91% (8q12) and 89% (8q16) of patients maintained their original randomized dosing interval with no shortening, and in the 8 mg-combined group, 93% of patients maintained a dosing interval ≥12 weeks. The mean change from baseline in total fluorescein leakage area at Week 48 was -9.2, -13.9, and -9.4 mm2 with 2q8, 8q12, and 8q16, respectively. Safety outcomes for aflibercept 8 mg and 2 mg were similar through Week 48.
Conclusions :
Aflibercept 8 mg met the primary efficacy endpoint in DME, demonstrating non-inferiority in BCVA vs aflibercept 2 mg, with no new safety signals through 48 weeks. The vast majority of patients maintained extended ≥12-week dosing (93% in 8 mg-combined) and 16-week dosing (89% in 8q16). Overall, aflibercept 8 mg provides greater therapeutic benefit, an expanded injection interval, and equivalent safety vs aflibercept 2 mg.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.