Aflibercept 8 mg Noninferior to Standard 2 mg Dose Through 48 Weeks in PHOTON Trial
Diana V. Do, MD, Professor of Ophthalmology and Vice Chair for Clinical Affairs at the Byers Eye Institute, Stanford University
Aflibercept 8 mg demonstrated noninferiority to aflibercept 2 mg, showed no safety concerns through 48 weeks, and met the primary efficacy endpoint for patients with diabetic macular edema (DME), according to Diana V. Do, MD, who recently presented her results at the 2023 Association for Research in Vision and Ophthalmology Annual Meeting in New Orleans, Louisiana.
The goal of the study was to evaluate the efficacy and safety of aflibercept 8 mg vs 2 mg in patients with DME.
The Phase 3 PHOTON trial (NCT04429503) is a double-masked, 96-week, noninferiority study that randomized patients with DME to receive either aflibercept 8 mg every 12 weeks (8q12; n = 328) or 16 weeks (8q16; n = 163) after three monthly doses or aflibercept 2 mg every 8 weeks after 5 monthly doses (2q8; n = 167). During Week 16 through 48, patients in the 8q12 or 16q12 groups received the novel treatment in shorter intervals if they met prespecified dose regimen modification criteria indicating disease activity.
The trial’s primary endpoint was the mean change from baseline in best-corrected visual acuity (BCVA) at Week 48 (noninferiority margin at four letters). The key secondary endpoint was the proportion of patients with ≥ two-step improvement in Diabetic Retinopathy Severity Scale (DRSS score) at Week 48 (noninferiority margin at 15%).
The results showed that aflibercept 8 mg met the trial's primary efficacy endpoint. The mean BCVA change from baseline at Week 48 was +9.2, +8.8, and +7.9 letters for those in the 2q8 group, 8q12 group, and 8q16 group, respectively (least squares mean difference: noninferiority p < 0.0001 for 8q12 vs 2q8 [95% CI: -2.26 to 1.13]; noninferiority p = 0.0031 for 8q16 vs 2q8 [95% CI: -3.27 to 0.39]).
The proportion of patients with ≥ two-step improvement from baseline in DRSS score was 27%, 29%, and 20% with 2q8, 8q12, and 8q16, respectively (8q12 group met the noninferiority margin of 15% [95% CI vs 2q8: -6.61 to 10.57], whereas the 8q16 group did not [95% CI vs 2q8: -16.88 to 1.84]).
Through Week 48, most patients in the 8q12 cohort (91%) and in the 8q16 cohort (89%) maintained their original randomized dosing intervals. 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.
“Overall, aflibercept 8 mg provides greater therapeutic benefit, an expanded injection interval, and equivalent safety vs aflibercept 2 mg,” Dr Do concluded.
Looking ahead, researchers submitted a data package to the FDA for aflibercept 8 mg for both DME and neovascular age-related macular degeneration. Dr Do noted that a decision from the FDA is expected soon.