Aflibercept 8mg Noninferior to Aflibercept 2mg in Diabetic Macular Edema

Aflibercept 8mg has achieved the primary efficacy endpoint in diabetic macular edema (DME) secondary to retinal vein occlusion (RVO), displaying noninferiority to aflibercept 2mg in best-corrected visual acuity (BCVA).

Presented at the 43rd Annual Scientific Meeting of the American Society of Retina Specialists in Long Beach, CA, by Seenu Hariprasad, MD, University of Chicago, these data stem from the QUASAR study, an ongoing, 64-week, randomized, double-blind, active-controlled phase 3 study involving patients ≥18 years of age with DME secondary to RVO (branch, central, or hemiretinal vein occlusion).1

Aflibercept has been compared to an entire complement of alternative therapies for DME in the past, with conflicting results. Even in individual trials, the consistency of aflibercept’s superiority to alternatives like ranibizumab has fluctuated from phase to phase. For instance, a randomized clinical trial of aflibercept, bevacizumab, and ranibizumab indicated the superiority of aflibercept at 1 year but relatively equal results between the 3 treatments at year 2.2

At the outset of QUASAR, patients were assigned 1:1:1 to receive 8q8/3, 8q8/5, or 2q4. Investigators could shorten the dosing regimens by 4 weeks for participants in the aflibercept 8q8/3 group from week 16 and for patients in the aflibercept 8q8/5 group from week 24. They could also extend by 4 weeks from week 32 for the 8q8/3 and 2q4 groups and from week 40 for the 8q8/5 group. All these extensions were based on defined modification criteria for shortening and extending dosing intervals. The minimum interval was every 4 weeks.1

QUASAR’s primary objective was to measure BCVA to determine if aflibercept 8mg provided a non-inferior change compared to 2q4. Investigators employed a non-inferiority margin of 4 letters. The primary endpoint was the change from baseline BCVA by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score at week 36. Secondary endpoints included the number of active injections from baseline, maintenance of every 8 weeks dosing in the aflibercept 8mg groups, change from baseline in central subfield retinal thickness (CRT), and safety through week 36.1

A total of 892 patients (8q8/3: n = 293; 8q8/5: n = 298; 2q4: n = 301) were randomly assigned to treatment. Mean (standard deviation [SD]) age was 65.9 +/- 11.6 years, and 47.8% of the patients were female. Aflibercept 8mg showed noninferior BCVA gains versus aflibercept 2mg, with mixed model for repeated measures (MMRM) based least squares (LS) mean difference (2-sided 95% CI) in BCVA versus 2q4 at week 36 of -.01 (-2 to 1.9) letters for 8q8/3 (P <.0001) and +.8 (-1.1 to 2.7) letters for 8q8/5 (P <.0001, 1-sided noninferiority test).1

Patients assigned to aflibercept 8mg achieved these BCVA gains with fewer injections compared to aflibercept 2mg (6 and 6.8 for 8q8/3 and 8q8/5, respectively, versus 8.5 for 2q4) over 36 weeks. The MMRM-based LS mean difference in CRT versus 2q4 at week 36 was -.1 (-10 to 9.8) and 1.2 (-7.7 to 10.2) µm for 8q8/3 and 8q8/5, respectively. Through week 36, 88.5% (8q8/3, n = 246) and 93.4% (8q8/5, n = 255) of patients who completed 36 weeks of treatment maintained dosing intervals of 8mg.1

Aflibercept 8mg’s safety profile was consistent with the established profile of aflibercept 2mg in patients with DME secondary to RVO. Hariprasad and colleagues noted a collective 91% of patients treated with aflibercept 8mg maintained 8-week dosing intervals. There were no new safety signals observed through week 36.1

“Overall, aflibercept 8mg provides robust visual outcomes with fewer active injections, and with a therapeutic benefit and safety profile that is comparable with aflibercept 2mg,” Hariprasad and colleagues wrote.1

References

1. Hariprasad S, Chaudhary V, Chen Y, Chang A, Kamei M, et al. Aflibercept 8 mg in Treatment-Naïve Macular Edema Secondary to Retinal Vein Occlusion: Primary Endpoint results From the QUASAR Study. Abstract presented at the 43rd Annual Scientific Meeting of the American Society of Retina Specialists in Long Beach, CA, July 30-August 2, 2025.

2. Wells JA, Glassman AR, Ayala AR, et al. Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema: Two-Year Results from a Comparative Effectiveness Randomized Clinical Trial. Ophthalmology. 2016;123(6):1351-1359. doi:10.1016/j.ophtha.2016.02.022