For generations, retina specialists have listened helplessly as patients with geographic atrophy described their frustrations about visual dysfunctions and anxieties about losing more vision. But our field wasn’t idle through those years. Teams of researchers methodically built upon insights from genetics, pathology, immunology, ocular imaging and clinical observation, finally yielding a tangible option for patients. 

Last month, with the Food and Drug Administration approval of pegcetacoplan (Syfovre, Apellis Pharmaceuticals) for treatment of GA, a new era dawned for retina. This is arguably the biggest innovation in retina care since anti-VEGF injections. 

With this new era, we face a host of new challenges and uncertainties. 

First, the efficacy benefit is modest. We would all like a drug that stopped GA growth, but that’s not what we have, at least not on average through two years. Specifically, in the OAKS and DERBY Phase III registration trials involving 1,258 patients, pegcetacoplan reduced GA growth 17 to 20 percent, with a greater benefit among eyes with nonsubfoveal GA, at 22 to 26 percent. Most importantly, efficacy increased over time, with up to a 30 percent reduction in GA growth over months 18 to 24. 

Simply put, this is a therapy that will likely need to be given indefinitely to yield maximal benefit, and there’s currently no biomarker we can use to measure efficacy. It’s important that patients understand these perspectives before they start therapy to appropriately set expectations. 

Second, pegcetacoplan has key side effects to recognize that appear dose-dependent. New wet AMD was diagnosed in 12, 7 and 3 percent of monthly, every-other-month and sham patients. Ideally, patients receive optical coherence tomography imaging regularly to screen for any evidence of exudation so that they can efficiently start anti-VEGF therapy when needed. 

Ischemic optic neuropathy was diagnosed in 1.7, 0.2 and 0 percent of the aforementioned arms, respectively. While we need more data about these patients, and data from large numbers of patients treated in routine clinical practice will likely prove valuable to better define and understand this potential risk signal, at this time one might consider every-othr-month dosing, particularly among patients at risk of ION due to a disc at risk and/or other factors. 

Practically, the volume and viscosity of pegcetacoplan are unique. Pegcetacoplan is a viscous fluid delivered as 100 µL. It requires substantially more time to draw into the syringe than our anti-VEGF agents. Be patient and use a Luer Lock syringe. Then, make sure the entire dose is delivered intravitreally before withdrawing the needle. Also, consider approaches to minimize intraocular pressure fluctuations, especially in high-risk eyes. 

The FDA-approval of pegcetacoplan validates complement as a therapeutic target in GA. It’s an exciting time in retina and we’re going to learn much more about pegcetacoplan and GA as we go forward. RS