Ursula Schmidt-Erfuth, MD: Effect of Pegcetacoplan on Photoreceptor Integrity


Presented at ASRS 2023, results from the GALE extension study showed crossover to pegcetacoplan treatment from sham stabilized photoreceptor degeneration over 6 months.

Optical coherence tomography (OCT)-based artificial intelligence analysis indicated pegcetacoplan treatment efficiently maintained photoreceptor integrity and prevented further degeneration in eyes with geographic atrophy (GA).

Results from the GALE extension of the pivotal phase 3 OAKS and DERBY studies showed crossover to pegcetacoplan treatment from sham was associated with a nearly 20% reduction in RPE loss and an approximately 100% reduction in photoreceptor degeneration in the first 6 months.

The findings were presented at the American Society of Retina Specialists (ASRS) 41st Annual Meeting in Seattle, Washington.

“The conclusion is that, yes, even advanced lesions will benefit largely from pegcetacoplan treatment,” presenting author Ursula Schmidt-Erfuth, MD, professor and chair of the department of ophthalmology at the Medical University of Vienna, told HCPLive at ASRS. “And that there are OCT-based precision tools that allow to measure the effect and to identify disease activity reliably.”

The prespecified analysis of the GALE extension study prospectively assessed the effect of intravitreal pegcetacoplan in sham-treated patients beginning pegcetacoplan therapy. Changes in photoreceptor and RPE layer integrity were assessed using deep learning analysis based on spectral-domain OCT

OCT volumes from SPECTRALIS SD-OCT were processed by deep-learning-based image analyses using validated algorithms identifying and quantifying PR loss and thinning. The RPE algorithm was consistent with lesion size measurements on fundus autofluorescence in OAKS and DERBY. Changes from baseline in photoreceptor degeneration and RPE loss area was analyzed using mixed-effects models for repeated measures methodology.

Approximately 75% of patients in OAKS and DERBY completed the studies; of these patients, approximately 83% rolled over into the GALE extension study. At the start of OAKS and DERBY, the investigators noted nearly one-third of GA lesions across all groups were in the largest tertial (≥9.655 mm2). By the start of GALE, approximately two-thirds of GA lesions across all patients were in the largest tertile.

Upon analysis, the data showed a clear reduction in the progression of photoreceptor degeneration between months 24 and 30 in patients who crossed over from sham to pegcetacoplan treatment (difference, -106.0%; P <.0001). Crossover to pegcetacoplan treatment showed an 18.8% reduction in RPE loss (P = .0153) and a 104.3% reduction in photoreceptor degeneration (P <.0001) in the first 6 months, compared to the prior 6 months of sham.

The investigative team noted the OCT-based AI analysis was reliable in identifying and quantifying the loss of photoreceptor and RPE layers in disease activity and therapeutic maintenance in patients with GA.

“We were able to provide proof of principle that disease activity can be identified using such AI-based photoreceptor and RPE imaging,” Schmidt-Erfuth told HCPLive. “This is now crucial in clinical practice, to identify the patients that will benefit from treatment because they have a larger ratio of photoreceptor versus RPE loss and also to monitor disease progression or non-progression.”

Relevant disclosures for Dr. Scmidt-Erfuth include Apellis, Genentech, and Kodiak.

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