Aflibercept 8 mg two-year results from pivotal PHOTON trial in diabetic macular edema presented at ASRS- Regeneron + Bayer

“At two years, the PHOTON trial demonstrates the substantial impact aflibercept 8 mg could have in reducing treatment burden for patients with diabetic macular edema,” said Diana V. Do, MD, Professor of Ophthalmology and Vice Chair for Clinical Affairs at the Byers Eye Institute, Stanford University and a trial investigator. “Maintaining two years of vision and anatomic improvements with as few as three or four injections per year, while not compromising safety, is impressive and could make a meaningful difference in the lives of the patients we treat.”

PHOTON (N=658) is a double-masked, active-controlled pivotal trial evaluating non-inferiority of aflibercept 8 mg extended dosing intervals compared to Eylea. Patients receiving aflibercept 8 mg were initially randomized to either 12- (n=328) or 16-week (n=163) dosing intervals (after three initial monthly doses) compared to an 8-week dosing regimen for Eylea (n=167) after five initial monthly doses. During the trial, patients receiving aflibercept 8 mg could have their dosing intervals shortened down to an every 8-week interval if protocol-defined criteria for disease progression were observed. Patients were only able to extend their dosing intervals in the second year by 4-week increments up to 24-weeks, if pre-specified criteria were met.

The PHOTON trial met its primary endpoint last year with aflibercept 8 mg patients achieving clinically equivalent vision gains to Eylea, with approximately 90% maintaining 12- and 16-week dosing regimens through the first year. Through two years, the mean number of injections administered were 9.5 for the 12-week aflibercept 8 mg group, 7.8 for the 16-week aflibercept 8 mg group, and 13.8 for the Eylea group, with the vast majority of aflibercept 8 mg patients maintaining extended dosing intervals as first shared in June 2023: i.89% of patients maintained greater than 12-week dosing intervals, compared to 93% through one year. ii. 84% maintained greater than 16-week dosing intervals, compared to 89% maintaining a 16-week dosing interval through one year, among those randomized at baseline to a 16-week dosing interval. iii.44% met the criteria for greater than 20-week dosing intervals at week 96, including 17% and 27% who were eligible for 20- and 24-week dosing intervals, respectively.

The safety of aflibercept 8 mg continued to be similar to Eylea through two years and remained consistent with the known safety profile of Eylea from previous clinical trials for DME. Ocular treatment emergent adverse events (TEAE) occurring in 5% of patients in any treatment group, in decreasing frequency, were cataract, vitreous floaters and conjunctival hemorrhage. There were no cases of retinal vasculitis, occlusive retinitis or endophthalmitis. The rate of intraocular inflammation was 1.2% for both the Eylea and aflibercept 8 mg groups. Anti-platelet trialists' collaboration-defined arterial thromboembolic TEAEs occurred in 7.2% of patients treated with Eylea and 6.7% of patients treated with aflibercept 8 mg.

The full ASRS presentation is available on the Regeneron website. The two-year data from the pivotal PULSAR trial for aflibercept 8 mg in wet age-related macular degeneration (wAMD) are expected in the third quarter of 2023.

Aflibercept 8 mg is investigational, and its safety and efficacy have not been fully evaluated by any regulatory authority. Aflibercept 8 mg is being jointly developed by Regeneron and Bayer AG, with Regeneron sponsoring the PHOTON trial. In the U.S., Regeneron maintains exclusive rights to Eylea and aflibercept 8 mg. Bayer has licensed the exclusive marketing rights outside of the U.S., where the companies share equally the profits from sales of Eylea and aflibercept 8 mg following any regulatory approvals.

About the Aflibercept 8 mg Clinical Trial Program : PULSAR in wAMD and PHOTON in DME are double-masked, active-controlled pivotal trials that are being conducted in multiple centers globally. In both trials, patients were randomized into 3 treatment groups to receive either: aflibercept 8 mg every 12 weeks, aflibercept 8 mg every 16 weeks, or Eylea every 8 weeks. The lead sponsors of the trials were Bayer for PULSAR and Regeneron for PHOTON.

Patients treated with aflibercept 8 mg in both trials had 3 initial monthly doses, and patients treated with Eylea received 3 initial doses in PULSAR and 5 in PHOTON. During the trial, patients in the aflibercept 8 mg groups could have their dosing intervals shortened down to an every 8-week interval if protocol-defined criteria for disease progression were observed. Intervals could not be extended until the second year of the study. Patients in all Eylea groups maintained a fixed 8-week dosing regimen throughout their participation in the trials.