On February 17, 2023, the drug pegcetacoplan (Syfovre; Apellis Pharmaceuticals) was approved by the US FDA as the first treatment for prevention of geographic atrophy (GA) progression. This is an amazing milestone in the retinal drug timeline. We owe a huge debt of gratitude to Apellis cofounder and CEO/president Cedric Francois, MD, PhD, and his team for their unfailing belief that complement inhibition would work when many in the community did not believe it would.

The green light for Syfovre does not come without controversy. There are some very bright and loud voices in our community that feel that the drug should not be used. They distort the clinical trial results to conclude that the slowed progression amounts to only a few months and only a few RPE cells. They correctly point out that the drug had no effect on functional outcomes during the pivotal trials. They also note some peculiar adverse events. In their minds, the risks outweigh the benefits.

On the other side of the coin is where most of us fall. We know that slowing progression of GA will prevent vision loss in the long run. The recently reported functional results from Iveric Bio’s avacincaptad pegol GATHER pivotal studies (C5 inhibitor under review by the FDA) illustrate this point. In these studies that started with nonfoveal GA lesions, treatment prevented 15-letter vision loss at 1 year, and it would be expected that this gap would increase over time. Thus, one explanation for the lack of functional results in the Apellis studies could be that most of the patients started out with subfoveal lesions and one can only truly show a functional benefit if there is function to save.

I am firmly in the camp that complement modulation is beneficial for our patients. In this issue we explore how to incorporate Syfovre into your practice. How to cope with the increase in injection volume and ways to use your staff to improve flow are discussed. Some big questions arise now. Who should receive treatment? How do we keep patients on the drug to maintain the benefits? Should we use this on a patient with a small subfoveal GA lesion? Recent presentations by Retinal Physician editorial board member Usha Chakravarthy, MD, suggest that unifocal, subfoveal lesions grow very rapidly and that maybe we should use the drug in these patients.

How often should it be delivered? There is not an imaging biomarker to determine treatment intervals like in wet AMD. Geographic atrophy progression is too slow to see changes month to month. In the absence of guidance, some have suggested using 6-week intervals. We will see others come up with other treatment intervals over the next few years. Until then, the interval decision will require a very frank discussion with our patients. If this were my eye, I would want monthly injections to get the greatest possible benefit at slowing progression. Moreover, we will see poor real-world outcomes if an appropriate interval is not maintained. Keeping patients on regular therapy will be vital but very difficult, and patient buy-in from the outset is required.

There are still many questions, and the answers will become clearer as our experience with the drug increases. It is a very exciting time in retina as we finally have a treatment for this huge unmet need, and I look forward to offering it to my patients. RP