Two-Year Results for Aflibercept 8 mg from PHOTON Trial Demonstrate Durable Vision Gains at Extended Dosing Intervals in DME
Regeneron released on Tuesday topline, 2-year (96 weeks) data for aflibercept 8 mg from the 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 2 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,” Jeffrey Heier, MD, Director of the Retina Service and Retina Research at Ophthalmic Consultants of Boston and a trial investigator, said in a company news release. “To be able to rapidly achieve extended dosing intervals without any sacrifice of vision gains over 2 years is a tremendous benefit in 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.
| Through 48 weeks (one year) | Through 96 weeks (two years) | ||||||||||||
| EYLEA 8-week regimen | aflibercept 8 mg 12-week regimen | aflibercept 8 mg 16-week regimen | EYLEA 8-week regimen | aflibercept 8 mg 12-week regimen | aflibercept 8 mg 16-week regimen | ||||||||
| Mean number of injections^ | 7.9 | 6.0 | 5.0 | 13.8 | 9.5 | 7.8 | |||||||
| Mean observed BCVA improvement, letters | 9.2 | 8.8 | 7.9 | 8.4 | 8.8 | 7.5 | |||||||
| LS mean (SE) change from baseline, letters | 8.7 (0.7) | 8.1 (0.6) | 7.2 (0.7) | 7.7 (0.9) | 8.2 (0.6) | 6.6 (0.8) | |||||||
| Difference in LS mean (95% CI), letters | -0.6* (-2.3, 1.1) | -1.4† (-3.3, 0.4) | +0.5‡ (-1.6, 2.5) | -1.1§ (-3.3, 1.1) | |||||||||
| Proportion of patients losing ≥15 letters, per LOCF | 1.2% | 2.1% | 0.6% | 3.6% | 3.4% | 1.2% | |||||||
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<0.0001
†Non-inferiority p-value: p=0.0031
‡Nominal non-inferiority p-value: p<0.0001
§Nominal non-inferiority p-value: p=0.0044
In PHOTON, the safety of aflibercept 8 mg also continued to be similar to Eylea through 2 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 2-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, MD, 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 2-year PHOTON results reinforce the potential of aflibercept 8 mg to become the standard of care for the treatment of diabetic macular edema.”
The 2-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 2-year data from both PHOTON and PULSAR are planned for presentation at an upcoming medical meeting.