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    Potential treatment for atrophic AMD on the horizon

    Apellis presented results from the phase III OAKS and DERBY studies in geographic atrophy.

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    Apellis presented results from the phase III OAKS and DERBY studies in geographic atrophy

    Over 50% of legal blindness in Australia is caused by age-related macular degeneration (AMD). Treatment for neovascular AMD is well established and its introduction coincided with reduced incidence of legal blindness and increased age at which Australians register as blind.1 Treatment for atrophic AMD, or geographic atrophy (GA), has remained elusive but recent clinical trial results look promising.

    Age-related macular degeneration is the leading cause of blindness and irreversible vision loss in Australia among older Australians, with over 50% of legal blindness caused by AMD. While treatment for neovascular AMD has been available for over a decade, there remains a substantial unmet medical need for treatment that can slow, halt or reverse geographic atrophy (GA).

    On 9th September 2021, Apellis announced results from two phase III trials that showed pegcetacoplan, a drug that inhibits the activation of complement component C3, slowed GA progression. The clinical trial results have now been presented at medical conferences in the USA.2,3

    OAKS4 and DERBY5 are largely identical 24-month, phase III, multicentre, randomized, double-masked, sham-injection controlled trials designed to assess the efficacy and safety of multiple intravitreal injections of pegcetacoplan in subjects with GA secondary to AMD. Participants were aged 60 years or more with visual acuity 6/96 (24 ETDRS letters) or better, foveal or extrafoveal lesions with total lesion area 2.5– 17.5mm². Patients were excluded if they had a history of active CNV, or RPE tear, in the study eye.

    Each study randomized patients to receive 15mg pegcetacoplan intravitreal injection either monthly or every other month or one of two corresponding sham treatment arms. The primary endpoint at 12 months was the change in total area of GA lesions in the study eye based on fundus autofluorescence imaging. Various secondary functional and imaging outcomes will be assessed at 24 months.

    A total of 1258 patients were included in the two studies. At 12 months, pegcetacoplan reduced lesion growth in a combined analysis by 14% (every-other-month eye injections) and 17% (monthly eye injections) compared with no treatment (sham injections). The treatment effect on extrafoveal lesions was 23% (every-other-month) and 26% (monthly) compared with sham.

    Treatment outcomes differed between the two studies. Whereas the OAKS trial reduced lesion growth by 16% (every other month) to 22% (monthly) (P<0.01), the DERBY study failed to meet the primary endpoint with lesion growth reduced by 11% (every other month) to 12% (monthly) (P=NS). In prespecified analyses a consistent efficacy of pegcetacoplan was observed in study eyes compared with untreated fellow eyes.

    Overall, pegcetacoplan intravitreal injection was well tolerated. There were few serious treatment-emergent ocular adverse events. Endophthalmitis rates were in line with previous clinical trials of intravitreal treatments. Intraocular inflammation was infrequent. New onset exudative AMD occurred in 6% of patients on monthly treatment, 4.1% of patients on every other month treatment, and 2.4% of sham treated patients. Patients that developed exudative AMD continued treatment with pegcetacoplan and were eligible to receive anti-VEGF therapy per label.

    Participants will continue in the studies until they have received dosing for 24 months. Prespecified secondary outcomes to be reported at that time include conventional and low-luminance best-corrected visual acuity, reading speed, NEI VFQ-25, functional reading independence and microperimetry (in OAKS only). Participants are eligible to enter the long-term GALE study and receive active treatment either monthly or every other month for up to 36 months.6

    These outcomes will offer better understanding of the longer term benefits and safety of treatment with pegcetacoplan. Apellis plans to submit the clinical trial results to regulatory authorities in the USA in 2022.


    1. Heath Jeffery et al Asia Pac J Ophthalmol 2021; 10: 442-449. doi: 10.1097/APO.0000000000000415
    2. Steinle et al. Efficacy of Intravitreal Pegcetacoplan in Geographic Atrophy: Results from the Phase 3 DERBY and OAKS Trials, ASRS 2021.
    3. Boyer et al. Safety of Intravitreal Pegcetacoplan in Geographic Atrophy: Results from the Phase 3 DERBY and OAKS Trials, ASRS 2021.
    4. Clinical Trials registry
    5. Clinical Trials registry
    6. Clinical Trials registry

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