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HomeminewsTreatment for GA Closer with Positive Phase-3 Study Results

Treatment for GA Closer with Positive Phase-3 Study Results

The first treatment for geographic atrophy (GA) may soon be available, following the announcement of positive top-line results from Phase 3 DERBY and OAKS studies evaluating intravitreal pegcetacoplan, an investigational targeted C3 therapy, developed by Apellis Pharmaceuticals.

The study involved 1,258 adults with GA secondary to age-related macular degeneration (AMD) and based on results, Apellis plans to submit a New Drug Application (NDA) for the therapy to the United States Food and Drug Administration (FDA) in the first half of 2022.

Pegcetacoplan demonstrated a clinically meaningful slowing of disease progression with an even stronger effect in GA patients with extrafoveal lesions

GA is a leading cause of blindness that impacts more than five million people globally.1,2 An advanced form of AMD, excessive complement activation drives irreversible lesion growth in GA,3 and C3 is the only target to precisely control complement over-activation.

“These results underscore the potential for pegcetacoplan to become the first treatment for geographic atrophy, a progressive and irreversible disease that robs patients of their vision and for which no treatment exists,” said Dr Jeffrey S. Heier, principal investigator of the DERBY study and director, retina service and director, retinal research, Ophthalmic Consultants of Boston. “Pegcetacoplan demonstrated a clinically meaningful slowing of disease progression with an even stronger effect in GA patients with extrafoveal lesions.”

Monthly and every-other-month treatment with pegcetacoplan met the primary endpoint in OAKS, significantly reducing GA lesion growth by 22% (p=0.0003) and 16% (p=0.0052), respectively, compared to pooled sham at 12 months. DERBY did not meet the primary endpoint, showing a reduction in GA lesion growth of 12% (p=0.0528) and 11% (p=0.0750) with monthly and every-other-month treatment, respectively, compared to pooled sham at 12 months. In a prespecified analysis of the combined DERBY and OAKS studies, monthly and every-other-month treatment with pegcetacoplan reduced GA lesion growth by 17% (p<0.0001) and 14% (p=0.0012), respectively, compared to pooled sham at 12 months.

In a prespecified analysis of the primary endpoint, pegcetacoplan demonstrated a greater effect in patients with extrafoveal lesions at baseline. Patients with GA typically present first with extrafoveal lesions, which then progress toward the fovea where central vision is impacted. In the combined studies, monthly and every-other-month treatment with pegcetacoplan decreased GA lesion growth by 26% (p<0.0001) and 23% (p=0.0002), respectively, in patients with extrafoveal lesions compared to pooled sham at 12 months.

“Our mission is to develop transformative therapies for people with complement-driven diseases and now, after decades of challenges in this complex disease, pegcetacoplan is the first investigational therapy to significantly slow the progression of GA in a large Phase 3 study,” said Professor Federico Grossi, chief medical officer, Apellis.

“Across our ophthalmology development program, pegcetacoplan has demonstrated an efficacy and safety profile with both monthly and every-other-month dosing that we believe supports treatment for GA patients. We look forward to working with regulatory authorities to bring this medicine to patients in need as quickly as possible.”

Pegcetacoplan was well tolerated in both Phase 3 studies. The pooled rate of new-onset exudations was 6.0% of patients in the monthly pegcetacoplan groups, 4.1% in the every-other-month pegcetacoplan groups, and 2.4% in the sham groups. Two cases of confirmed infectious endophthalmitis and one case of suspected infectious endophthalmitis were observed in the study eye out of a total of 6,331 injections (0.047%). Thirteen events of intraocular inflammation were observed in the studies (0.21% per injection). No events of retinal vasculitis or retinal vein occlusion were observed. There were no clinically relevant changes in vision for patients who developed infectious endophthalmitis or intraocular inflammation.

“On the heels of our recent FDA approval in PNH, these pivotal results further reinforce the platform potential of targeting C3 across multiple diseases with few or no treatments,” said Cedric Francois, M.D., Ph.D., co-founder and chief executive officer, Apellis. “Apellis is singularly positioned to make a meaningful difference for patients living with a broad range of retinal, rare, and neurological diseases by targeting C3 to comprehensively control complement.”

The company continues to analyse results from the studies, and detailed data will be presented at upcoming scientific meetings.


DERBY (621 patients enrolled) and OAKS (637 patients enrolled) are Phase 3, multicentre, randomised, double-masked, sham-controlled studies comparing the efficacy and safety of intravitreal pegcetacoplan with sham injections in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The primary objective of the studies is to evaluate the efficacy of pegcetacoplan in patients with GA assessed by change in the total area of GA lesions from baseline as measured by fundus autofluorescence (p-value less than .05) at 12 months. Patients in DERBY and OAKS will continue on masked treatment for 24 months.


Pegcetacoplan is an investigational, targeted C3 therapy designed to regulate excessive activation of the complement cascade, part of the body’s immune system, which can lead to the onset and progression of many serious diseases. Pegcetacoplan was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of geographic atrophy.

1 Rudnicka AR, Jarrar Z, Wormald R, et al. Age and gender variations in age-related macular degeneration prevalence in populations of European ancestry: a meta analysis. Ophthalmology 2012;119:571–580.
2 Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health 2014;2:e106–116. 3 Seddon, JM, Rosner, B. Validated prediction models for macular degeneration progression and predictors of visual acuity loss identify high-risk individuals. Am J Ophthalmol 2019;198:223–261.


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