Thomas Jefferson University
David Brown, MD from Retina Consultants of Texas presented results from the Phase 2/3 PHOTON trial examining the efficacy and safety of 8 mg aflibercept compared to 2 mg aflibercept in patients with diabetic macular edema. Dr. Brown opened the talk by discussing the socioeconomic challenges that many patients living with diabetes may have. He noted that needing frequent injections to treat DME only adds to the burden in many patients. A larger dose that is administered less frequently would therefore may be beneficial.
In the PHOTON trial, a novel formulation of aflibercept was used that packaged a 4-fold higher molar dose into a 70 uL injection. A total of 685 patients were enrolled and were randomized into three separate study arms in a 1:2:1 ratio: in the first arm, aflibercept 2 mg was dosed every 8 weeks after 5 initial monthly injections (2q8 group), in the second, 8 mg aflibercept was given every 12 weeks after 3 initial monthly injections (8q12 group), and in the third, 8 mg aflibercept was given every 16 weeks after 3 initial monthly injections (8q16 group). The primary endpoint was the mean change in BCVA, and secondary endpoint was the proportion of patients with a with 2-step improvement in the diabetic retinopathy severity score at week 48. Further criteria were established for shortening the dose regimen intervals if there was both a greater than 10-letter loss in BCVA and greater than 50 um increase in central retinal thickness.
Notably, all three groups were similar in composition. The baseline A1c for all three groups was about 8.0, and other demographics such as race, gender, and age were similar among all three groups. The mean number of injections up until week 48 was 7.7 in the 2q8 group, 5.7 in the 8q12 group, and 4.9 in the 8q16 group.
Importantly, both 8 mg groups met the primary endpoint at week 48 and were non-inferior to the control 2q8 group. In terms of the secondary endpoint, much of the benefits of aflibercept was observed from the initial monthly dosing. At 12 weeks, the proportion with a 2-step improvement in DRSS was 26% in the 2q8 group, 25% in the 8q12 group, and 21% in the 8q16 group and at 48 weeks was 27%, 29%, and 21% respectively. The groups receiving aflibercept 8 mg achieved similar mean changes in central retinal thickness (CRT) by week 48. When examining individual matched intervals at multiple time points, the 8 mg aflibercept groups experienced less rebound in CRT than the 2q8 groups. Significantly, a large majority of the patients maintained their dosing regimen with 91% maintaining a q12 dosing and 89% of patients maintaining a q16 dosing (in their respective cohorts). Overall, 93% of 8 mg patients maintained a dosing interval of 12 weeks.
Importantly, there were no significant differences in adverse outcomes such as endophthalmitis, occlusive retinal vasculitis, the number of APTC events, hypertension events, and deaths among each group. Furthermore, despite using a larger 70 uL injection in the 8 mg groups, there was no significant increase in intraocular pressure.