Jennifer I. Lim, MD: Effect of Faricimab on nAMD with Pigment Epithelial Detachments

Dual angiopoietin-2 (Ang-2)/vascular endothelial growth factor (VEGF)-A inhibition with faricimab was linked to improved persistent epithelial detachment (PED) outcomes versus aflibercept among patients with neovascular age-related macular degeneration (nAMD), according to an analysis presented at the 127th Annual American Academy of Ophthalmology (AAO) Meeting in San Francisco, California.

Results showed, after the head-to-head dosing phase of the phase 3 TENAYA and LUCERNE studies, reductions in max PED thickness and the resolution of serous PED favored faricimab versus aflibercept. Safety was additionally in favor of faricimab, with a well-tolerated safety profile comparable with aflibercept through the end of the study.

“This is important because when we look at TENAYA and LUCERNE overall, we also found the same thing – that faricimab dried these eyes better in terms of resolution of intraretinal and subretinal fluid better than aflibercept,” said Jennifer I. Lim, MD, Marion H. Schenk Chair in Ophthalmology, University of Illinois at Chicago, in an interview with HCPLive. “This speaks to the fact that dual inhibition of Ang-2/VEGF-A is a better drying agent than just anti-VEGF alone.

Approximately 30–80% of patients with nAMD have PED, and it is often more difficult to resolve than intraretinal (IRF) or subretinal fluid (SRF). PED in nAMD requires more consistent anti-VEGF therapy and can recur during pro re nata treatment.

The head-to-head dosing phase of the phase 3 TENAYA and LUCERNE studies indicated greater anatomic improvements with faricimab treatment, versus aflibercept, regarding change in central subfield thickness (CST) and absence of IRF and SRF. Patients treated with faricimab up to Q16W also achieved the first absence of IRF and SRF with fewer injections at Week 8, than aflibercept Q8W at Week 12 (hazard ratio [HR], 1.47; 95% CI, 1.24 - 1.73; P <.0001).

Lim’s analysis assessed if dual Ang-2/VEGF-A inhibition with faricimab would improve PED versus aflibercept. Most patients in TENAYA and LUCERNE had PED involving the foveal center at baseline. Among those with PEDs at baseline, approximately 80% of PEDs at baseline were fibrovascular.

The analysis assessed the reduction in max PED thickness with faricimab versus aflibercept in the head-to-head dosing phase. At Week 12, the difference in adjusted mean thickness for faricimab versus aflibercept was –13.5 µm (95% CI, –23.2 to –3.7).

Investigators also assessed the reduction in max fibrovascular PED thickness with faricimab versus aflibercept in the head-to-head dosing phase. At week 12, the difference in adjusted mean thickness was –10.0 µm (95% CI, –20.8 to 0.8).

Moreover, fewer patients had the presence of serious PEDs with faricimab treatment versus aflibercept at Week 12, with a difference of –8.4% (95% CI, –14.7 to –2.0; P = .0258). The reduction in max serous PED thickness between faricimab and aflibercept revealed a difference of –27.9 µm (95% CI, –50.3 to –5.5) at Week 12.

Regarding safety, retinal pigment epithelium (RPE) tears were associated with larger baseline PED heights and more frequently occurred after 1–3 anti-VEGF injections. Most events were considered nonserious, mild, and reported as unrelated to the study drug and did not result in sustained vision loss. Approximately half of the patients with RPE tears had fibrovascular PED and most had an occult choroidal neovascularization at baseline.

For more insight into the analysis, watch the full interview with Dr. Lim.

References

_{Lim JI, Margaron P, Souverain A, Yang M, Kotecha A, Willis JR, Patel S, Khanani AM, Bakri SJ. How Effective Is Anti-ANG2 and Anti-VEGF (Faricimab) for Neovascular AMD With Persistent Epithelial Detachments?. Presented at the 2023 American Academy of Ophthalmology Annual Meeting, November 3 – 6, 2023.}