Of approved GA treatments,

SYFOVRE has the longest continuous thread of clinical evidence in GA secondary to AMD^1-3

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Trial Designs
OAKS and DERBY Baseline

“A WIDE RANGE OF GA PATIENTS WERE SELECTED FOR THE CLINICAL TRIALS”

“Given that a wide range of GA patients were selected for the clinical trials, what are the key considerations when selecting patients for SYFOVRE treatment in clinical practice?”

Dr Jeremy Wolfe, MD addresses this question using a real patient case from his own practice. Watch the full video to learn about his approach and the importance of patient motivation.

“A WIDE RANGE OF GA PATIENTS WERE SELECTED FOR THE CLINICAL TRIALS”

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Selecting Appropriate Patients for SYFOVRE

INDICATION

SYFOVRE® (pegcetacoplan injection) is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

SYFOVRE is contraindicated in patients with ocular or periocular infections, in patients with active intraocular inflammation, and in patients with hypersensitivity to pegcetacoplan or any of the excipients in SYFOVRE. Systemic hypersensitivity reactions (e.g., anaphylaxis, rash, urticaria) have occurred.

Please stay tuned for additional Important Safety Information and please see accompanying full Prescribing Information.

Introduction

Hi, I'm Jeremy Wolfe. I'm a Retina Specialist in Royal Oak, Michigan. I practice in a large, retina-only group, where we see a number of patients with all retinal diseases, especially patients with macular degeneration and geographic atrophy.

I’m going to share some insights from my own experience with SYFOVRE treatment over the past year. I’ll focus on my approach to selecting appropriate patients with GA for SYFOVRE treatment.

SYFOVRE Clinical Trials: Inclusion Criteria

The SYFOVRE Phase 3 clinical trials included a broad range of patients with GA, as we can see in these scans from the patients who participated in the trials.

Patients who had lesions either with or without subfoveal involvement were included in the trials, as were patients with multifocal or unifocal GA lesions.

In the trials, all patients were only treated in one eye. If both eyes had GA lesions, the eye with worse vision received SYFOVRE treatment.

GA, choroidal neovascularization, or both were permitted in the untreated fellow eye.

In clinical practice, patients with bilateral GA can be treated in either eye, or both eyes.

So, given that a wide range of GA patients were selected for the clinical trials, what are the key considerations when selecting patients for SYFOVRE treatment in clinical practice? And what factors apply to selecting which eye, or eyes, to treat?

Let’s look at a patient from my own practice who I’ve treated with SYFOVRE, so I can show my own approach to addressing these questions.

This patient is an 89-year-old woman who I first examined about 2 years ago. Her main ophthalmic findings included bilateral GA and, in her right eye, neovascular AMD.

Let’s look at some scans from that initial visit.

On the FAF scans shown here, we can see that the GA in her right eye already had subfoveal involvement. And in addition to that subfoveal GA, the right eye has neovascular AMD.

For the neovascular AMD in the right eye, I initiated treatment with anti-VEGF injections.

At presentation, this patient’s left eye had GA, but without subfoveal involvement.

Prior to treatment, the right eye was the worse-seeing eye, with a BCVA of 20/200.The left eye retained relatively good vision at 20/25.

At the time of presentation, when these scans were taken, SYFOVRE was not available to treat GA.

Now, let’s look at OCT scans of both of her eyes over the next 2 years.

On the left are scans from her initial visit. And on the right, we have scans captured 2 years later.

After two years, vision in the patient’s right eye had deteriorated to 20/800. I attribute the change in vision to the progression of GA. In the right eye, you can see the expansion of the GA lesion over time in the widening of the white area of choroidal hypertransmission indicating areas of atrophy, indicated here with the white brackets.

In the left eye also, over 2 years there was progression of the GA lesions, which were now beginning to encroach on the fovea.

In the left eye, the patient's excellent baseline vision experienced a slight decline after two years, and we can see in the scans the GA lesion progressing closer towards the foveal center.

The visual decline in her left eye was more noticeable than it might have been because the vision in her right is so bad. The right eye can't fill in the area that's missing in the left eye.

Currently, a large portion of the patients with GA that I treat with SYFOVRE are patients like this one—patients that I am already treating for neovascular AMD.

I find these patients are often ideal candidates for SYFOVRE treatment because they are already coming to my practice at regular intervals for treatment and monitoring of their neovascular AMD. And they have already received regular intravitreal injections, so they understand the process, and are comfortable with the means of administration.

This group was represented in clinical trials as well. While none of the patients in the trials had choroidal neovascularization in the study eye, per the exclusion criteria, roughly 20% of the patients included had choroidal neovascularization in the fellow eye at baseline.

It’s important to note here that SYFOVRE was associated with increased rates of neovascular AMD in the clinical trials, and that patients receiving SYFOVRE should be monitored for signs of neovascular AMD. In case anti-VEGF treatment is required, it should be given separately from SYFOVRE administration.

Starting the Treatment Discussion

Using the scans, I explained the irreversible damage that started in a part of the macula has progressed to involve more and more of the area involved in visual function.

This is when I began the discussion about treatment with SYFOVRE.

The Importance of Patient Motivation

I try to select patients who are motivated and invested in the opportunity to get treatment for their GA. The patient we looked at earlier was highly motivated to seek treatment. In fact, we had already been discussing the possibility of GA treatments in development in 2023.

Additional motivation came from having already experienced substantial vision loss in one eye—the right eye that had both neovascular AMD and subfoveal GA. This patient was in a position to really want to delay, if possible, similar devastation in her left eye, where she still maintained decent visual acuity, although with some symptoms in the form of a noticeable central scotoma.

As I mentioned earlier, patients with neovascular AMD who have experience with regular intravitreal injections have the potential to be excellent candidates for treatment of GA with SYFOVRE.

This patient is a great example. Because of her 2-year history with neovascular AMD, she was quite familiar with intravitreal injections, and we had the opportunity, with SYFOVRE’s flexible dosing, to work treatment for GA into her current schedule of visits to the practice.

For any patient considering SYFOVRE treatment, I go over the results of the SYFOVRE phase 3 clinical trials, which compared lesion growth rates in patients who received SYFOVRE monthly and every other month to patients who got a sham injection, where an empty syringe without a needle was pressed to the eye.

Based on these studies, we have data showing slower lesion growth rates over two years in both SYFOVRE treatment arms compared to patients not receiving SYFOVRE. It's important to manage expectations with patients, so they understand that SYFOVRE involves ongoing treatment that may help slow the future growth of their GA lesions but will not stop or reverse existing damage.

And, of course, I make sure the patient understands the risk of adverse events that may come with SYFOVRE injections.

The Treatment Discussion

We decided to treat this patient’s left eye with SYFOVRE.

SYFOVRE has a flexible dosing schedule of one injection once every 25-60 days.

We chose a 6-week interval for the SYFOVRE injections because that fits well into her current scheduled visits for treatment and monitoring of the neovascular AMD in the fellow eye.

Here are the scans from her first three visits for SYFOVRE injections to the left eye.

As expected for these relatively short intervals, there was minimal observable change to the lesions.

While we made the decision to treat this patient in the better-seeing left eye that didn’t have neovascular AMD, in other patients with bilateral GA, I have initially made the decision to treat the worse-seeing eye.

Ultimately, the decision to treat with SYFOVRE and the choice of which eye or eyes to start on treatment will be different for each appropriate patient with GA. The extent of lesion progression, the impact of GA on vision, and the patient’s motivation all need to be considered.

The data from the Phase 3 clinical trials showed reduced lesion growth compared to sham with 2 years of SYFOVRE treatment. This is a long-term course of therapy, and the importance of selecting patients who are likely to stay on treatment for the long term should not be underestimated. This is a highly motivated patient whom I hope will experience safe and efficacious treatment with SYFOVRE for years.

INDICATION

SYFOVRE^® (pegcetacoplan injection) is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

SYFOVRE is contraindicated in patients with ocular or periocular infections, in patients with active intraocular inflammation, and in patients with hypersensitivity to pegcetacoplan or any of the excipients in SYFOVRE. Systemic hypersensitivity reactions (e.g., anaphylaxis, rash, urticaria) have occurred.

WARNINGS AND PRECAUTIONS

Endophthalmitis and Retinal Detachments
- Intravitreal injections, including those with SYFOVRE, may be associated with endophthalmitis and retinal detachments. Proper aseptic injection technique must always be used when administering SYFOVRE to minimize the risk of endophthalmitis. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately.
Retinal Vasculitis and/or Retinal Vascular Occlusion
- Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, have been reported with the use of SYFOVRE. Cases may occur with the first dose of SYFOVRE and may result in severe vision loss. Discontinue treatment with SYFOVRE in patients who develop these events. Patients should be instructed to report any change in vision without delay.
Neovascular AMD
- In clinical trials, use of SYFOVRE was associated with increased rates of neovascular (wet) AMD or choroidal neovascularization (12% when administered monthly, 7% when administered every other month and 3% in the control group) by Month 24. Patients receiving SYFOVRE should be monitored for signs of neovascular AMD. In case anti-Vascular Endothelial Growth Factor (anti-VEGF) is required, it should be given separately from SYFOVRE administration.
Intraocular Inflammation
- In clinical trials, use of SYFOVRE was associated with episodes of intraocular inflammation including: vitritis, vitreal cells, iridocyclitis, uveitis, anterior chamber cells, iritis, and anterior chamber flare. After inflammation resolves, patients may resume treatment with SYFOVRE.
Increased Intraocular Pressure
- Acute increase in IOP may occur within minutes of any intravitreal injection, including with SYFOVRE. Perfusion of the optic nerve head should be monitored following the injection and managed as needed.

ADVERSE REACTIONS

Most common adverse reactions (incidence ≥5%) are ocular discomfort, neovascular age-related macular degeneration, vitreous floaters, conjunctival hemorrhage.

Please see accompanying full Prescribing Information.

SYFOVRE offers an unprecedented breadth of long-term experience^1-4

Longest continuously enrolled GA programs^1-3

2-year Phase 3 trials & ongoing 3-year extension trial ^2,4

Largest enrollment^1-3

>1200 patients⁴*

Most injections¹

>23,000 injections^1†

Reflective of GA patients who may be seen in real-world clinical practice¹

Lesions with and without subfoveal involvement^‡
With and without history of or active CNV in the fellow eye
Unilateral and bilateral GA
Unifocal and multifocal lesions
Broad range of lesion sizes (2.5 mm² to 17.5 mm²)

*1258 patients randomized among SYFOVRE and sham treatment groups in OAKS and DERBY.⁴

^†23,437 SYFOVRE injections administered across 1111 patients randomized among monthly and EOM treatment groups in OAKS and DERBY, and through 2 years of GALE, including patients who crossed over to monthly or EOM treatment from sham.¹

^‡Lesions without subfoveal involvement defined as distance >0 µm from the atrophy junction to the foveal center.¹

Of approved GA treatments,

Only SYFOVRE has 4 years of continuous trial data^1-3

Scroll to see full chart → Scroll to see more

Safety and efficacy were evaluated in two Phase 3 trials and an ongoing extension trial^1,2,4

OAKS and DERBY 2‑year,
double-masked trials⁴

TRIAL ASSESSMENT:

Change from baseline in rate of GA lesion area growth measured by FAF

Explore OAKS and DERBY efficacy results >

PATIENTS WITH GA SECONDARY TO AMD (N=1258)⁴

Randomized 2:2:1:1

83% OF PATIENTS WHO COMPLETED OAKS OR DERBY CONTINUED IN GALE^§ (N=780)^||

SYFOVRE
MONTHLY
(n=419)

SYFOVRE
EOM
(n=420)

SHAM
MONTHLY
(n=208)

SHAM
EOM (n=211)

Sham groups pooled for analysis (n=419)

GALE 3-year, open-label, extension trial²

TRIAL ASSESSMENTS:

Incidence and severity of ocular and systemic adverse events (AEs)
Change from baseline in the total area of GA lesion(s) in study eye (mm²)

Explore GALE efficacy results >

SYFOVRE
MONTHLY
(n=241)

SYFOVRE
EOM
(n=268)

CONTINUED TREATMENT

SYFOVRE
MONTHLY
(n=129)

SYFOVRE
EOM
(n=144)

PREVIOUSLY UNTREATED

Over 1100 patients with GA have received SYFOVRE across the Phase 3 clinical program¹

^§First GALE visit was required to be within 60 days of the final OAKS and DERBY visit.¹

^‖Ten patients from Phase 1b Study 103 enrolled in GALE and are included in the safety analysis.¹

GALE is a long-term, ongoing, open-label, multicenter, Phase 3 extension study, subject to patient dropouts over time
The analysis for GALE utilized a projected sham and may not reflect rate of change of all patients with GA
Mean rate of change of projected sham from Year 2 to Year 3 and Year 3 to Year 4 was estimated from the mean rate of change in each 6-month period from Year 0 to Year 2 in the sham group
Analyses from GALE are prespecified but there is no statistical testing hierarchy; therefore, the results need cautious interpretation
Open-label studies can allow for selection bias
- Of note, the 24-month lesion growth rate reduction vs sham pooled for those that continued into GALE was similar to the overall patient population from OAKS and DERBY

Scroll to see full chart →

SYFOVRE® (pegcetacoplan injection) OAKS and DERBY baseline characteristics icon

Baseline patients and study eye characteristics¹

OAKS

SYFOVRE
MONTHLY
(n=202)

SYFOVRE
EOM
(n=205)

SHAM
POOLED
(n=207)

DERBY

SYFOVRE
MONTHLY
(n=201)

SYFOVRE
EOM
(n=201)

SHAM
POOLED
(n=195)

PATIENT CHARACTERISTICS

Mean age (years)

Female

62%

57%

64%

59%

60%

63%

Male

38%

43%

36%

41%

40%

37%

Caucasian

92%

91%

93%

96%

Fellow eye CNV

21%

18%

21%

19%

20%

19%

GEOGRAPHIC REGION

73%

69%

71%

61%

63%

ROW

27%

31%

29%

39%

37%

STUDY EYE CHARACTERISTICS

Mean GA lesion size

8.2 mm²

8.3 mm²

8.2 mm²

8.4 mm²

8.3 mm²

8.2 mm²

GA lesion size <7.5 mm²

50%

48%

50%

49%

GA lesion location without subfoveal involvement

43%

36%

29%

36%

40%

37%

GA lesion focality unifocal

29%

30%

33%

27%

26%

34%

Bilateral GA

83%

85%

80%

82%

80%

77%

Number of intermediate/large drusen >20

46%

51%

50%

39%

50%

Pseudodrusen (NIR)

83%

87%

84%

89%

90%

85%

Mean BCVA score

Mean LLD*—ETDRS letters

*LLD at baseline was available for 199, 199, and 192 patients in the monthly, EOM, and sham groups, respectively, in DERBY.¹

A broad range of patients were included¹

Key inclusion criteria

GA lesion requirements:
- Total size: 2.5 mm² to 17.5 mm²
- With and without subfoveal lesion involvement
- If multifocal, at least 1 focal lesion must be ≥1.25 mm²
- Presence of perilesional hyperautofluorescence
Age ≥60 years
BCVA ≥24 letters using ETDRS charts in the study eye

Key exclusion criteria

GA secondary to a condition other than AMD such as Stargardt disease in either eye
History of or active CNV in the study eye, including presence of RPE rips (assessed by reading center)
Prior participation in any other interventional clinical study for GA in either eye

Among agents approved to treat GA, only SYFOVRE was studied in trials that allowed patients with subfoveal lesions in the study eye or CNV in the fellow eye^1,5

OAKS and DERBY

In OAKS, 31% of patients in the monthly group, 21% of patients in the every other month and 25% of the patients assigned to sham discontinued treatment prior to Year 2. In DERBY, 29% of patients in the monthly group, 22% of patients in the every other month and 21% of the patients assigned to sham discontinued treatment prior to Year 2.⁴

The most frequent reasons for discontinuation from treatment were consent withdrawal (10%), death (4%), adverse events (4%), and COVID-19 impact (4%).¹

Among all patients enrolled in OAKS and DERBY who received at least one injection of SYFOVRE or sham, 75% completed their respective study through Year 2 (n=940/1256).¹

GALE

Through Years 1 and 2 of GALE, 18.4% of patients in the continued monthly group, 23.0% of patients in the continued EOM group, 24.0% of patients in the sham monthly to SYFOVRE monthly group, and 20.1% of patients in the sham EOM to SYFOVRE EOM group discontinued treatment.¹

The most frequent reasons for discontinuation were consent withdrawal (9.2%), death (5.2%), and adverse events (3.2%).¹

Only SYFOVRE is approved for both monthly and EOM dosing in GA^4,6*

*The recommended dose for SYFOVRE is 15mg (0.1mL of 150mg/mL solution) administered by intravitreal injection to each affected eye once every 25 to 60 days.⁴

AMD=age-related macular degeneration; BCVA=best-corrected visual acuity; CNV=choroidal neovascularization; EOM=every other month; ETDRS=Early Treatment Diabetic Retinopathy Study; FAF=fundus autofluorescence; GA=geographic atrophy; LLD=low-luminance deficit; RPE=retinal pigment epithelium; ROW=rest of world.

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References: 1. Data on file. Apellis Pharmaceuticals, Inc. 2. Wykoff CC, Holz FG, Chiang A, et al; OAKS, DERBY, and GALE Investigators. Pegcetacoplan treatment for geographic atrophy in age-related macular degeneration over 36 months: data from OAKS, DERBY, and GALE. Am J Ophthalmol. 2025; 276:350-364. doi:10.1016/j.ajo.2025.04.016. 3. Khanani AM, Patel SS, Staurenghi G, et al; GATHER2 trial investigators. 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;402(10411):1449-1458. doi:10.1016/S0140-6736(23)01583-0. 4. SYFOVRE (pegcetacoplan injection) [package insert]. Waltham, MA: Apellis Pharmaceuticals, Inc.; 2025. 5. 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. 6. IZERVAY™ (avacincaptad pegol intravitreal solution) [package insert]. Northbrook, IL: Astellas Pharma, US Inc.; 2025.

SYFOVRE has the longest continuous thread of clinical evidence in GA secondary to AMD^1-3

“A WIDE RANGE OF GA PATIENTS WERE SELECTED FOR THE CLINICAL TRIALS”

“A WIDE RANGE OF GA PATIENTS WERE SELECTED FOR THE CLINICAL TRIALS”

SYFOVRE offers an unprecedented breadth of long-term experience^1-4