Spotlight on SYFOVRE®

This Spotlight Series article is editorially independent content.

Geographic atrophy (GA) is the advanced form of age-related macular degeneration (AMD) and the leading cause of blindness worldwide. The prevalence of GA increases markedly with age, impacting more than 1 million Americans and 5 million individuals worldwide. It is a progressive and irreversible disease caused by the growth of lesions, which destroy the retinal cells responsible for vision.^1,2 Data has shown that, on average, it takes only 2.5 years for GA lesions to start impacting the fovea, which is responsible for central vision.³

 SYFOVRE®: A Novel Therapy

Until recently, ophthalmologists have not had a viable option to treat GA, presenting a considerable gap in patient care. Clinical trials are underway investigating potential therapeutics including complement inhibitors, neuroprotective agents, ocular gene therapy, and stem cell therapy.⁴

In February 2023, the US Food and Drug Administration (FDA) approved the first treatment for GA. SYFOVRE (pegcetacoplan injection; Apellis Pharmaceuticals, Inc) is a complement inhibitor indicated for the treatment of GA secondary to AMD.⁵

Efficacy Data

SYFOVRE has been studied in multiple clinical trials, demonstrating slowed GA progression.

OAKS and DERBY Studies

The FDA approved SYFOVRE based on the results from the OAKS and DERBY studies at 24 months across a broad and representative population of patients. OAKS and DERBY were 24-month, multicenter, randomized, double-masked, sham-controlled, phase 3 studies that included 1,258 patients.⁶

The studies evaluated the efficacy of SYFOVRE administered monthly and every other month (EOM) in patients with GA, assessed by change in the total area of GA lesions from baseline. Patients with GA (atrophic nonexudative AMD), with or without subfoveal involvement, secondary to AMD were randomized 2:2:1:1 to receive the following for 2 years:⁶

• SYFOVRE 15 mg/0.1 mL intravitreally monthly
• SYFOVRE EOM
• Sham monthly
• Sham EOM

The findings showed a clinically meaningful reduction of GA lesion growth with increasing effects over time in both the SYFOVRE monthly and EOM dosing arms versus the sham arms. GA lesion growth after 1 and 2 years of treatment with SYFOVRE are illustrated in the FIGURE below.⁶

GALE Extension Study

SYFOVRE also demonstrated increasing treatment effects over time in the GALE extension study following 3 years of continuous treatment with SYFOVRE. GALE was a multicenter, open-label, phase 3 extension study that evaluated the long-term efficacy and safety of SYFOVRE. Patients included in the analyses were in the SYFOVRE treatment arms through month 24 in the OAKS and DERBY studies and remained on the same regimen in GALE.⁷

The results demonstrated reductions in GA lesion growth and nonsubfoveal GA lesion growth with SYFOVRE monthly and EOM between months 24 and 36 versus the sham arms (see FIGURES below).⁷

GALE Total Population Cohort: Reduction in GA Growth Following 36 Months of Continuous Pegcetacoplan (Compared With Sham)

GALE Nonsubfoveal Subgroup (n=286 eyes): Reduction in GA Growth Following 36 Months of Continuous Pegcetacoplan (Compared With Sham)

Safety and Tolerability

SYFOVRE has a well-demonstrated safety profile following approximately 12,000 injections over 24 months.⁵ In a combined analysis of the OAKS and DERBY studies, the most common adverse reactions (≥5%) reported in patients receiving SYFOVRE were:⁸

• Ocular discomfort
• Neovascular AMD
• Vitreous floaters
• Conjunctival hemorrhage

Additionally, the safety profile in the first 12 months of the GALE extension study was similar to that observed in the OAKS and DERBY studies.⁷

Dosing

SYFOVRE is available in single-use vials. The recommended dose for SYFOVRE is 15 mg (0.1 mL of 150 mg/mL solution) administered by intravitreal injection to each affected eye once every 25 to 60 days. Ophthalmologists should ensure that the injection is given immediately after the preparation of the dose.⁸

For more information, visit https://syfovreecp.com.

References

1. Vujosevic S, Alovisi C, Chakravarthy U. Epidemiology of geographic atrophy and its precursor features of intermediate age-related macular degeneration. Acta Ophthalmol. 2023;101(8):839-856. doi:10.1111/aos.15767
2. Rahimy E, Khan MA, Ho AC, et al. Progression of geographic atrophy: retrospective analysis of patients from the IRIS^® Registry (Intelligent Research in Sight). Ophthalmol Sci. 2023;3(4):100318. doi:10.1016/j.xops.2023.100318
3. Lindblad AS, Lloyd PC, Clemons TE, et al; Age-Related Eye Disease Study Research Group. Change in area of geographic atrophy in the Age-Related Eye Disease Study: AREDS report number 26. Arch Ophthalmol. 2009;127(9):1168-1174. doi:10.1001/archophthalmol.2009.198
4. Khan H, Aziz AA, Sulahria H, et al. Emerging treatment options for geographic atrophy (GA) secondary to age-related macular degeneration. Clin Ophthalmol. 2023;17:321-327. doi:10.2147/OPTH.S367089
5. FDA approves SYFOVRE™ (pegcetacoplan injection) as the first and only treatment for geographic atrophy (GA), a leading cause of blindness. News release. Apellis Pharmaceuticals, Inc. February 17, 2023. Accessed February 3, 2025. https://investors.apellis.com/news-releases/news-release-details/fda-approves-syfovretm-pegcetacoplan-injection-first-and-only
6. Heier JS, Lad EM, Holz FG, et al; OAKS and DERBY study investigators. Pegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration (OAKS and DERBY): two multicentre, randomised, double-masked, sham-controlled, phase 3 trials. Lancet. 2023;402(10411):1434-1448. doi:10.1016/S0140-6736(23)01520-9
7. Wykoff CC, Heier JS, Jones D, Yemanyl F, Nakabayashi M. Long-term efficacy and safety of pegcetacoplan from the GALE open-label extension of the phase 3 OAKS and DERBY trials. Poster presented at the American Academy of Ophthalmology Annual Meeting; November 3-6, 2023; San Francisco, CA.
8. Package insert. Apellis Pharmaceuticals, Inc; 2024.