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Subspecialties Retina

Stopping The Unstoppable

The slow progression of geographic atrophy (GA) has made the identification of viable treatment options challenging. But by specifically targeting complement C3, the newly FDA-approved treatment SYFOVRE (pegcetacoplan injection) from Apellis provides control of the complement cascade, a critical component of the body’s immune system. (1)

The approval follows positive results from the DERBY and OAKS studies, which compared the efficacy and safety of SYFOVRE with sham injections across a varied population of patients with GA. After a 24 month period, SYFOVRE was found to reduce the rate of GA lesion growth compared with sham.

We sat down with Caroline Baumal, Chief Medical Officer at Apellis, and CEO and cofounder Cedric Francois,to talk about what this new treatment means for the retina space – and for patients.

What inspired you to take on a disease as challenging as GA?

Francois: Well, there is an incredible unmet medical need; more than a million patients in the US alone are affected by this disease. It is typically something that patients start seeing or acquiring around the age of 70 and above. These are the last decades of life where you have the chance to watch your grandchildren or great grandchildren grow up. Going blind can have a dramatic and terrible impact on our lives, so giving even a couple of extra years of vision to people is incredibly inspiring.

What is notable about this new treatment?

Baumal: Cedric has already noted the impact that GA has on independence and the quality of life for our elderly patients. But then consider that, prior to the approval of SYFOVRE, there were no treatments for GA.

Following the FDA approval? SYFOVRE is now available for all patients with GA, regardless of lesion location or whether one or both eyes are affected – and that’s reflective of the broad and representative population enrolled in our clinical trials. I’m really pleased with the dosing flexibility of every 25-60 days, which allows us to treat patients mirroring the clinical study regimens. The approval of SYFOVRE is a genuine scientific breakthrough and provides an advance for patients who have been waiting a long time for a treatment.

Looking at the bigger picture, the approval of SYFOVRE is the first definitive proof that the natural progression of GA can be modified, essentially turning GA into a treatable disease. We can intervene at the level of C3 and C3b in the complement cascade to slow down the disease progression.

Francois: It’s the first time after many failures that we have a drug that can slow down the progression of GA lesions. We’re going to look at further increasing efficacy over time; the aim is always to slow down progression of the disease as much as possible. We will also focus on convenience – in fact, we are already working on a pre-filled syringe that will make it easier for physicians to administer the product. But we will also try to find ways to reduce the frequency of the injections. Right now, we have very good efficacy with injections every two months – but perhaps we can go even lower.

Ultimately, there are two really important features that people need to know about. First, it has increasing effects over time, which is exceedingly rare. If you ask a physician to think about a drug that has an increasing effect over time, most won’t come up with a single example. Second, the dosing flexibility Caroline mentioned – from 25–60 days between injections. Just think about the practicality of that; when a patient needs to book an appointment, you have a whole month to play with!

What were the main challenges during development and approval?

Francois: Where do I even start?! Whenever a therapeutic goes through development, there are numerous challenges that must be overcome – and you need a series of small miracles to make it happen. But two particular challenges stand out. When we started the phase III clinical trial, we had a small manufacturing issue that caused a big headache – and we had limited time to fix things. We discovered the problem in September 2018 but still managed to restart clinical trials in March 2019. Another key challenge was when the DERBY trial missed the primary endpoint in phase III. At the time, statisticians offered interesting feedback about an important imbalance; in short, we had aggressive patients in the active arm compared with the sham control. At the time, it was very clear that if we treated these patients longer, the imbalance would correct itself – but, two months into the trial, the patients in the drug arm were 20 percent worse than the control.

It was a challenge but also a lesson. We learned that the drug needed more time to overcome the deficit to show its maximum potential. Amazingly, at 24 months into DERBY and OAKS the difference between the groups had gone.

What lies beyond the FDA approval?

Baumal: The US FDA approval is just the beginning of what’s possible for SYFOVRE. We continue to evaluate the long-term safety and efficacy of SYFOVRE in the GALE extension study, which is a three-year trial. Combined with the phase III DERBY and OAKS studies, GALE will allow us to better understand the efficacy and safety profile of SYFOVRE with up to five years of treatment. We are excited about this data and look forward to continuing to share information about this first-of-its-kind treatment with the medical community.

We are committed to bringing SYFOVRE to patients around the world as quickly as possible. In addition to our recent approval in the US, we are preparing for other approvals and launches; we have a marketing application that is currently under review in the European Union.

I am excited to be part of the team to bring SYFOVRE to patients as the first and only treatment for GA. As a retina specialist, I look forward to finally having a treatment to offer patients!

While SYFOVRE is exciting for the retinal space, recent concerns over safety events associated with the drug were voiced by the American Society of Retinal Specialists in July.

Apellis has been conducting a thorough evaluation following these reported events, the company states, including a review of the SYFOVRE manufacturing process. There were no changes in the formulation of the product between phase 3 clinical trials and commercial supply. Based on this review, the company adds, there is no indication that drug product or manufacturing issues contributed to these events, and there were no new safety findings in the clinical trials upon secondary review.

Since launch, Apellis has confirmed a total of seven  events of retinal vasculitis (four occlusive, three non-occlusive) as determined by the company’s internal safety committee and external retina/uveitis specialists. Two of these events followed injections in April, two in May, and three in June. Apellis is also evaluating one reported event of retinal vasculitis, which the company has not confirmed.

CEO Cedric Francois commented, “The safety of patients has always been – and continues to be – our top priority at Apellis. Following 68,000 commercial vials distributed and 23,000 clinical trial injections to date, these events continue to be very rare. Additionally, as part of our ongoing review, we have seen no indication that drug product or manufacturing issues contributed to these events. We will continue to collaborate with the retina community to deliver a safe, effective treatment for GA…” (2).

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  1. Apellis. “FDA Approves SYFOVRE™ (pegcetacoplan injection) as the First and Only Treatment for Geographic Atrophy (GA), a Leading Cause of Blindness” (2023). Available at:
  2. Apellis, “Apellis Provides Update on Review of Rare Safety Events with SYFOVRE® (pegcetacoplan injection) for Geographic Atrophy” (2023). Available at:
About the Author
Sarah Healey

Communicating stories in a way that is accessible to all was one of the focal points of my Creative Writing degree. Although writing magical realism is a fun endeavor (and one I still dabble in), getting to the heart of human stories has always been the driving motivator behind my writing. At Texere, I am able to connect with the people behind scientific breakthroughs and share their stories in a way that is impactful and engaging.

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