Roger A. Goldberg, MD: Impact of Dual Inhibition on Hard Exudates in DME

Dual angiopoietin-2/vascular endothelial growth factor (VEGF)-A inhibition with faricimab achieved numerically greater reductions in hard exudates than aflibercept in eyes with diabetic macular edema (DME), according to an exploratory analysis presented at the 2024 Association for Research in Vision and Ophthalmology (ARVO) Meeting.

The analysis included nearly 1900 patients from the pivotal phase 3 YOSEMITE and RHINE trials and could reflect improvements in vascular stability identified with faricimab treatment determined in other biomarker analyses.

In an interview with HCPLive, investigator Roger A. Goldberg, MD, a vitreoretinal surgeon at Bay Area Retina Associates, described how patients with hard exudates exhibited no difference between the treatment arms after the loading phase. However, those treated with faricimab saw a notable reduction in hard exudates at the 52-week and 96-week marks.

“If you look at year 1 and year 2, we see about a 10% reduction in the portion of patients who have no lipid hard exudates in the faricimab-treated eyes versus the aflibercept 2 mg-treated eyes,” Goldberg told HCPLive. “This suggests that faricimab, over time, does a better job at resolving hard exudates.”

Study participants were randomized 1:1:1 to receive intravitreal injections of faricimab 6.0 mg every 8 weeks (Q8W) or treat-and-extend (T&E) or aflibercept 2 mg Q8W. The presence of hard exudates was determined by a central reading center using color fundus photography within the ETDRS grid at screening and visits at 16 weeks, 52 weeks, and 96 weeks.

Evaluation for hard exudates was performed in 1870 patients from YOSEMITE and RHINE, with a similar proportion of patients with baseline hard exudates across all treatment arms (80.8 to 81.6%). Over time, the proportion of patients with hard exudates decreased during the study period.

Among those with hard exudates at baseline, the proportion at week 16 was similar between the faricimab and aflibercept treatment arms. At baseline to week 52, fewer patients treated with faricimab Q8W (79.0%) and T&E (86.2%) exhibited hard exudates versus patients treated with aflibercept (86.2%). This result remained at week 96 (52.8% and 55.9% vs. 64.5%).

Overall, these data corresponded to a difference of –7.2% (95% CI, –12.2 to –2.2; P = .0058) and –10.5% (95% CI, –15.6% to –5.4%; P <.0001) for faricimab Q8W and T&E at 52 weeks compared with aflibercept. Differences of –11.7% (95% CI, –18.6% to –4.8%; P = .0013) and –8.9% (95% CI, –15.7 to –2.1%; P = .0124) were identified at 96 weeks.

According to Goldberg, based on previous biomarker analyses, eyes with macular leakage may benefit from faricimab compared with other agents for DME. He noted these data indicate a similar biomarker-based decision to reach for faricimab in the presence of hard exudates.

“Similarly, I think clinically, when we see a lot of lipid hard exudates, that suggests this isn’t an eye with a lot of vascular instability and perhaps reaching for faricimab with its dual inhibition may be a better choice for these patients,” Goldberg told HCPLive.

Roger A. Goldberg, MD reports relevant consultant fees and financial support from Apellis, Boehringer Ingelheim, Genentech Inc., Regeneron, and others.

References

_{Goldberg RA, Amador M, Dinah C, Gibson K, Glittenberg C, Maunz A, O’Leary O, Rahimy E, Uschner D. Greater reduction in hard exudates with faricimab vs aflibercept in patients with DME: biomarker results from the phase 3 YOSEMITE/RHINE trials. Poster presented at the Association for Research in Vision and Ophthalmology (ARVO) 2024 Meeting, May 5–9, 2024.}