Ursula Schmidt-Erfurth, MD: Therapeutic Effect of Pegcetacoplan on GA Disease Activity

At ARVO 2023, Schmidt-Erfurth discusses new insights regarding disease activity in GA, observing reductions in both RPE and photoreceptor degeneration after intravitreal pegcetacoplan therapy in the OAKS and DERBY trials.

Ursula Schmidt-Erfurth, MD | Medical University of Vienna

Ursula Schmidt-Erfurth, MD

Credit: Medical University of Vienna

Intravitreal pegcetacoplan was linked to reductions in both retinal pigment epithelium (RPE) and photoreceptor degeneration in patients with geographic atrophy (GA) in the phase 3 OAKS and DERBY trials, according to new research.

The data, presented at the 2023 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting, suggested artificial intelligence (AI)-based optical coherence tomography (OCT) testing can accurately identify and quantify the loss of RPE and photoreceptor layers in disease activity and therapeutic response in GA.

“We learned from it in the context of a new therapy that is now available that we should include patients to the treatment that do have disease activity because they have the opportunity to show a therapeutic benefit,” Ursula Schmidt-Erfurth, MD, Professor and Chair, Department of Ophthalmology and Optometry, Medical University of Vienna told HCPLive at ARVO 2023. “We learn that the effect of complement inhibition is much biggest than just a handful of RPE cells, but that it is a very substantial preservation of photoreceptors from degeneration.”

The analysis looked to contribute new insight into the mechanism and outcomes of intravitreal pegcetacoplan, a complement C3 and C3b inhibitor, in eyes with GA, based on the results of DERBY and OAKS. To do so, investigators assessed the effect of intravitreal pegcetacoplan compared to sham in the changes in the area of RPE and photoreceptor loss using deep learning analysis of spectral domain-OCT (SD-OCT) images over 2-years of follow-up.

Individuals were randomized 2:2:1:1 into pegcetacoplan monthly (PM), pegcetacoplan every-other-month (PEOM), sham monthly, and sham monthly and sham EOM treatment over 2 years. in year 1, SD-OCT monitoring was conducted monthly. In year 2, SD-OCT monitoring was conducted monthly for PM and sham monthly groups and conducted every other month for the PEOM and sham EOM groups.

OCT volumes from Spectralis SD-OCT (n = 436 patients in OAKS; n = 433 patients in DERBY) were processed by deep learning image analyses using validated algorithms based on convolutional neural networks identifying the loss of RPE layer and ellipsoid zone defined as photoreceptor layers. Investigators analyzed the change from baseline through Month 24 in RPE and photoreceptor loss using mixed models for repeated measures methodology.

After 24 months of therapy, the analysis showed RPE and photoreceptor degeneration were significantly and consistently reduced in both trials as evaluated by SD-OCT. In the OAKS trial, data showed RPE loss was reduced by 22% (P = .0002) in PM versus sham pooled and by 20% (P = .0002) in PEOM versus sham pooled. Additionally, investigators found photoreceptor loss was reduced in PM versus sham pooled by 53% (P <.0001) and in PEOM versus sham pooled by 45.7% (P <.0001).

Moreover, in the DERBY trial, the progression of RPE loss was reduced in PM versus sham pooled by 27% (P <.0001) and in PEOM versus sham pooled groups by 21.2% (P = .0005). The analysis showed photoreceptor loss was reduced in PM versus sham pooled by 47.0% (P <.0001) and in PEOM versus sham pooled by 45.8% (P <.0001).

For more insight into the analysis of pegcetacoplan’s effect on RPE and photoreceptor integrity in GA, check out the full interview with Schmidt-Erfurth.

Ursula Schmidt-Erfurth, MD reports having received consultant fees and/or financial support from Apellis, Genentech, Novartis, Roche, and others.


Schmidt-Erfurth U, Mai J, Reiter GS, Vogi WD, Sadeghipour A, McKeown AS, Bogunovic H. Therapeutic effect of pegcetacoplan on retinal pigment epithelium (RPE) and photoreceptor (PR) integrity in geographic atrophy (GA) in the phase III OAKS and DERBY trials. Presented at the 2023 Association for Research in Vision and Ophthalmology Annual Meeting; April 2023; New Orleans, LA.

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