ARVO 2023: Data outlines Phase 3 functional analyses of pegcetacoplan injection for geographic atrophy

The analyses were reported during oral presentations at the Association for Research in Vision and Ophthalmology Annual Meeting in New Orleans. (Image courtesy of Ernest N. Morial Convention Center)

Apellis Pharmaceuticals Inc. announced post hoc analyses from the 24-month, Phase 3 OAKS and DERBY studies evaluating pegcetacoplan injection (Syfovre) for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

The analyses were reported during oral presentations at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting in New Orleans.

According to the company, pegcetacoplan injection showed visual function and quality-of-life benefits in patients with extrafoveal lesions (≥ 0.25 mm from the foveal center). Additionally, pegcetacoplan injection showed a meaningful reduction in the loss of photoreceptor and retinal pigmented epithelial (RPE) cells, which are both required for vision. These analyses utilized data from patients with SPECTRALIS optical coherence tomography (OCT) images, which allowed for artificial intelligence (AI)-based automated segmentation of the photoreceptor and RPE layers as well as determination of the amount of the central foveal region covered by the GA lesion (foveal occupancy).

Moreover, pegcetacoplan injection demonstrated visual function and quality-of-life benefits in patients with extrafoveal lesions.

In the 24-month analysis, pegcetacoplan injection-treated patients compared to sham demonstrated:

• Preservation of 5.6 letters, equivalent to more than one line of vision on an ETDRS chart, as measured by best corrected visual acuity (BCVA).
• A 4.1-point benefit in vision-related quality-of-life outcomes, as measured by the NEI-VFQ-25. The questionnaire assesses outcomes, such as social function, driving, and dependency on others. Four points is considered clinically meaningful.1

“Vision loss caused by GA can profoundly impact a person’s independence and well-being, so it is vital that pegcetacoplan injection has shown slower vision loss and better quality of life compared to sham in this post hoc analysis. These data also support earlier treatment with pegcetacoplan injection,” said Allen Chiang, MD, presenting author and associate professor of ophthalmology at Wills Eye Hospital, Mid Atlantic Retina, and Thomas Jefferson University.

Due to sample size considerations, every-other-month and monthly data from OAKS and DERBY were combined for the pegcetacoplan injection (n=131) and sham (n=61) groups. These data are in addition to the functional benefit outcomes previously reported in the post hoc junctional zone microperimetry analysis.

Pegcetacoplan injection also slowed photoreceptor and RPE cell loss compared to sham.

In the 24-month analysis of OAKS (n=456) and DERBY (n=435), pegcetacoplan injection demonstrated a meaningful reduction in the loss of both photoreceptor and RPE cells compared to sham (all p-values nominal):

• Photoreceptor cells
• Every-other-month: 46% (OAKS; p<0.0001) and 46% (DERBY; p<0.0001)
• Monthly: 53% (OAKS; p<0.0001) and 47% (DERBY; p<0.0001)
• RPE cells
• Every-other-month: 20% (OAKS; p=0.0002) and 21% (DERBY; p=0.0005)
• Monthly: 22% (OAKS; p=0.0002) and 27% (DERBY; p<0.0001)

RPE cells maintain the integrity of photoreceptor cells, and both types of cells are required for vision. Data were consistent when comparing pegcetacoplan injection-treated study eyes to the untreated fellow eyes.

“We are proud to share these data as part of our eight presentations at this year’s ARVO meeting, which showcase our leadership in GA and retina,” said Caroline Baumal, MD, chief medical officer at Apellis. “Syfovre is a gamechanger for GA as the first and only treatment for this relentless disease, and we look forward to exploring its potential to treat other complement-driven retina diseases with significant unmet needs.”

Marketing applications are currently under review with five regulatory agencies worldwide. A decision in the EU is expected in early 2024, and decisions in Canada, Australia, Switzerland, and the United Kingdom are expected in the first half of 2024.

OAKS (n=637) and DERBY (n=621) are Phase 3, multicenter, randomized, double-masked, sham-controlled studies comparing the efficacy and safety of pegcetacoplan injection with sham injections across a broad and heterogenous population of patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The studies evaluated the efficacy of monthly and every-other-month pegcetacoplan injection in patients with GA assessed by change in the total area of GA lesions from baseline as measured by fundus autofluorescence.

In Phase 3 studies at 24 months, both every-other-month and monthly pegcetacoplan injection reduced GA lesion growth with increasing effects over time and showed a well-demonstrated safety profile.