Regeneron Announces Two-year Results for Aflibercept 8 mg from Pivotal PHOTON Trial Demonstrate Durable Vision Gains at Extended Dosing Intervals in Diabetic Macular Edema

Regeneron Pharmaceuticals, Inc. (REGN) today announced top-line, two-year (96 weeks) data for aflibercept 8 mg from the pivotal PHOTON trial in patients with diabetic macular edema (DME). During the trial, aflibercept 8 mg patients were initially randomized to either 12- or 16-week dosing intervals (after three initial monthly doses) and were able to shorten or extend dosing intervals if pre-specified criteria were met. The longer-term data among aflibercept 8 mg patients who completed the trial demonstrated that the vast majority of patients were able to maintain or further extend these dosing intervals through two years with:

• 89% maintaining ≥12-week dosing intervals through two years, compared to 93% through one year (48 weeks)
• 83% maintaining ≥16-week dosing intervals through two years, compared to 89% maintaining a 16-week dosing interval through one year
• 43% meeting the criteria for ≥20-week dosing intervals by week 96, including 16% and 27% who were eligible for 20- and 24-week dosing intervals, respectively

“The two-year PHOTON results for aflibercept 8 mg in patients with diabetic macular edema are extremely compelling,” said Jeffrey Heier, M.D., Director of the Retina Service and Retina Research at Ophthalmic Consultants of Boston and a trial investigator. “To be able to rapidly achieve extended dosing intervals without any sacrifice of vision gains over two years is a tremendous benefit in the treatment of diabetic macular edema.”

“The two-year PHOTON results certainly exceeded my expectations and indicate that the majority of patients may eventually be able to control their diabetic macular edema with as few as two or three aflibercept 8 mg injections per year, if approved by regulatory authorities, with similar excellent visual gains and a safety profile consistent with EYLEA given every 8 weeks,” said David M. Brown, M.D., FACS, Director of Research at Retina Consultants of Texas and a trial investigator. “Reducing the treatment burden in patients with diabetic macular edema is a critical unmet need, and the two-year PHOTON results reinforce the potential of aflibercept 8 mg to become the standard of care for the treatment of diabetic macular edema.”

PHOTON (N=658) is a double-masked, active-controlled pivotal trial evaluating non-inferiority of aflibercept 8 mg 12-week (n=328) and 16-week (n=163) dosing regimens after three initial monthly doses compared to an 8-week dosing regimen for EYLEA (aflibercept) Injection (n=167) after five initial monthly doses. In addition to the vast majority of trial patients maintaining extended dosing intervals through two years, visual gains for aflibercept 8 mg remained consistent with the first year of the trial.

BCVA: best corrected visual acuity; LS: least squares; SE: standard error; LOCF: last observation carried forward
^Based on patients completing week 48 or 96 in the trial
*Non-inferiority p-value: p^†Non-inferiority p-value: p=0.0031
^‡Nominal non-inferiority p-value: p^§Nominal non-inferiority p-value: p=0.0044

In PHOTON, the safety of aflibercept 8 mg also 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 6.5% of patients treated with aflibercept 8 mg.

“The aflibercept 8 mg clinical trial program is the first to demonstrate that patients with diabetic macular edema can immediately be treated with every 12- or 16-week dosing after their initial monthly doses and experience lasting vision control,” said George D. Yancopoulos, M.D., Ph.D., Board Co-Chair, President and Chief Scientific Officer at Regeneron, and a principal inventor of EYLEA. “With these two-year results, Regeneron continues to raise the bar in clinical advancements for retinal treatments and remains committed to pursuing groundbreaking innovations in ophthalmology.”

The two-year data from the pivotal PULSAR trial for aflibercept 8 mg in wet age-related macular degeneration are expected in the third quarter of 2023, and the two-year data from both PHOTON and PULSAR are planned for presentation at an upcoming medical meeting.

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. In the first year, 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.