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Anti-complement injections have become a more common treatment for geographic atrophy (GA) secondary to dry AMD since pegcetacoplan (Syfovre, Apellis) and avacincaptad pegol (Izervay, Astellas) were approved by the FDA in March 2023 and August 2023, respectively. However, several myths remain regarding these medications.

Myth #1: Getting anti-complement injections will stop the disease.

It is important to remember that anti-complement injections will not halt progression of disease. Unfortunately, to date, no therapies halt GA or reverse disease. However, pegcetacoplan and avacincaptad pegol can help slow progression of disease and preserve retinal function for as long as possible.

Myth #2: Getting anti-complement injections will improve my patients’ vision.

Again, anti-complement injections simply slow the rate of progression of GA, and these rates vary depending on the drug, location of the lesion, and duration of therapy. Although there have been anecdotes from patients who feel as though their vision is improving with therapy, it is important to keep in mind that anti-complement drugs only slow the rate of GA progression. While the phase 3 trials for both pegcetacoplan and avacincaptad pegol did not show visual acuity benefits in prespecified endpoints,¹ the goal is to slow the onset or degree of vision loss.

Myth #3: There is no visual benefit to getting these injections

Recently from a prespecified endpoint in the GALE data—the extension study looking at the treatment of GA with pegcetacoplan—we learned that patients developed fewer new scotomatous points within 36 months in the continuous monthly and continuous every-other-month arm as compared to patients from the sham crossover group.² Post-hoc analysis of the GATHER trials, which looked at the treatment of GA with avacincaptad pegol, showed that treatment with avacincaptad pegol delayed the risk of progression to persistent vision loss compared to sham at one year.³ While we certainly would like to see more impressive visual acuity results, these signals are encouraging.

Myth #4: The risks of these medications are exceedingly high

This is a tricky one because all retina specialists have different thresholds of safety with which we are comfortable. There are risks to these medications. Both drugs pose a risk of conversion to wet macular degeneration, and all injections have a risk of endophthalmitis.^4,5 Beyond that, there have been reports of inflammation and nonarteritic ischemic optic neuropathy with pegcetacoplan use and rare reports of inflammation with avacincaptad pegol use in both respective clinical trials.^4,5 In the real world, we have also seen cases of retinal vasculitis/occlusive retinal vasculitis associated with pegcetacoplan use.⁶ That being said, the risk of GA must be weighed against the risks of the injection. For many patients, the almost certain risk of GA progression and vision loss is more frightening than the rare but possible risks of injections.

References

1. Csaky KG, Miller JML, Martin DF, Johnson MW. Drug approval for the treatment of geographic atrophy: how we got here and where we need to go. Am J Ophthalmol. 2024 Jul;263:231-239. doi: 10.1016/j.ajo.2024.02.021
2. Apellis Pharmaceuticals, Inc. SYFOVRE® (pegcetacoplan injection) preserved visual function at 36 months in GALE extension study in geographic atrophy (GA). Accessed June 18, 2024. https://investors.apellis.com/news-releases/news-release-details/syfovrer-pegcetacoplan-injection-preserved-visual-function-36.
3. Danzig CJ, Khanani AM, Kaiser PK, et al. Vision loss reduction with avacincaptad pegol for geographic atrophy: a 12-month post hoc analysis of the GATHER1 and GATHER2 trials. Ophthalmol Retina. 2024 May 6:S2468-6530(24)00224-0. doi:10.1016/j.oret.2024.04.023
4. Heier JS, Lad EM, Holz FG, et al. 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 Oct;402(10411):1434-1448. doi:10.1016/S0140-6736(23)01520-9
5. Khanani AM, Patel SS, Staurenghi G, et al. Efficacy and safety of avacincaptad pegol in patients with geographic atrophy (GATHER2): 12-month results from a randomised, double-masked, phase 3 trial. Lancet. 2023 Oct;402(10411):1449-1458. doi:10.1016/S0140-6736(23)01583-0
6. Witkin AJ, Jaffe GJ, Srivastava SK, Davis JL, Kim JE. Retinal vasculitis after intravitreal pegcetacoplan: report from the ASRS Research and Safety in Therapeutics (ReST) Committee. J Vitreoretin Dis. 2023 Dec;8(1):9-20. doi:10.1177/24741264231220224. Erratum in: J Vitreoretin Dis. 2024 Feb;8(3):363. doi:10.1177/24741264241238212

Priya Vakharia, MD is a member of Vit Buckle Society, the AAO, and the American Society of Retina Specialists. She practices at Retina Vitreous Associates of Florida in Palm Harbor and St. Petersburg.