High-Dose Eylea Offers Longer Treatment Intervals Across Patient Populations with DME

The high-dose, 8-milligram (mg) formulation of Eylea (aflibercept) continued to show gains in best-corrected visual acuity (BCVA) at 96 weeks across all patient subgroups with diabetic macular edema (DME) enrolled in the phase 3 PHOTON trial, according to study findings presented at the 2024 annual meeting of American Academy of Ophthalmology (AAO).

Sean D. Adrean, M.D.

"When we look at 8 mg aflibercept, all of these patients were able to maintain meaningful BCVA as we compare them from baseline to week 96, and most patients were able to maintain a dosing interval of 12 weeks or longer, and sometimes going out 16, 20, or 24 weeks, which was the cap," Sean D. Adrean, M.D., of Retina Consultants of Orange County in Fullerton, California, said during a presentation of the results.

The patients retained this level of vision with fewer injections, Adrean said, “and it is important to note that in all of these subgroup analyses, all of these patients are behaving similarly."

The PHOTON trial randomly assigned patients to be treated with the original 2-mg dose of Eylea every eight weeks or an 8-mg dose every 12 or 16 week. The primary end point was noninferiority in BCVA at 48 weeks, but the study continued for another 48 weeks, to week 96, with the option to continue if needed. The assessment Adrean presented was from the week 96 analysis.

The FDA approved the 8-mg dose in August 2023, and Regeneron is marketing that dose as Eylea HD.

Across all groups, nearly half of patients had received a prior treatment for DME before entering the study (44.2%). The age of patients was 62.3 years and the central retinal thickness (CRT) at baseline was similar, at 45 microns, in each arm. The BCVA at study entry was 61.5 letters in the 2-mg, 8-week interval control group and 63.6 and 61.4 in the 12-week and 16-week groups, respectively.

Using a mixed model for repeated measures, the mean change in BCVA letters at week 96 was calculated as +7.7 in the control group. In the 12-week arm, the mean change was +8.2 letters, which represented a +0.45 difference with the control arm, which met the standard for statistical significance for noninferiority. Compared with the control arm, there was a -1.1 difference in letters in the 16-week group, with a mean change of +6.6 letters, which was also deemed significant for noninferiority

Adrean and his colleagues analyzed the PHOTON results by race and other subgroups.

Nearly three-quarters (71.6%) of the participants in the study were White patients, 15.3% were Asian and 9.4% were Black or African American. For ethnicity, 18.1% reported being Hispanic or Latino. Among White participants, the BVCA gains were +7.9, +9.3, and +8.2 for those in the every 8-, 12-, and 16-week interval groups, respectively. The number of Asian participants in the trial was relatively small, but the results met the standard for statistical significance and were comparable to the results for the White participants. The Black or African American subgroups were too small did for proper evaluation and were not presented.

For those with Hispanic or Latino ethnicity, the mean change in BCVA was +8.7 in the control arm and +10.4 in the 12-week group. In the 16-week group, the average change in BCVA letters was +5.8. In the non-Hispanic or Latino groups, the results were similar across arms at +8.4, +8.6, and +7.8 letter changes in the control, 12-week interval and 16-week interval groups.

Similar findings were seen in analyses that grouped the patients in other ways. Among those who started the study with poorer vision — a baseline BCVA of 73 letters or less — the average change in letters was +9.4 in the control group and +9.6 and +8.1 in the 12-week and 16-week arms, respectively. Among those with better vision — a baseline BCVA of more than 73 letters — the control arm saw a +2 change in letters over the study period while the high-dose groups saw +5.9 and +4.3 changes, respectively.

Overall, 89% of patients enrolled in the 8-mg aflibercept group maintained a dosing interval of every 12 weeks or more.

By race, 93% of Asians maintained a dosing interval of every 12 weeks or more while 88% of White patients maintained that interval. In the Hispanic or Latino group, 99% of patients received the 8-mg dose every12 weeks or more. In the non-Hispanic or Latino group, 87% of patients received treatment for 12 weeks or more.

Of those with a CRT of 400 microns of less at baseline, 96% received a high dose aflibercept at least every 12 weeks, with 4% receiving it every 8 weeks. The dosing interval was at least 12 weeks for 85% of patients with CRT of more than 400 microns, with the remaining receiving treatment every 8 weeks.