Jump to:

Primary endpoint dataPost hoc US-only data24-Month dataPost hoc vision dataTrial designCase studySafety

Primary endpoint data

IZERVAY provided significant protection of healthy retinal cells in just one year of treatment²

IZERVAY reduced the annualized rate of GA lesion growth in two Phase 3 trials²

The efficacy and safety of IZERVAY were demonstrated in 2 randomized, multicenter, double-masked, sham-controlled, 18-month and 24-month studies in patients with GA due to AMD. The primary endpoint evaluated the mean rate of GA growth (slope) from baseline to Month 12, measured by FAF at 3 time points (baseline, Month 6, and Month 12). In GATHER2, the mean rate of GA growth (slope) measured by FAF was evaluated at 2 additional time points (Month 18 and Month 24).²

Reductions in mean rate of growth (MMRM analysis) at 12 months vs sham²

Graph of efficacy data from GATHER1 Study: 35% reduction in mean rate of GA growth at 12 months

Graph of efficacy data from GATHER2 Study: 18% reduction in mean rate of GA growth at 12 months

AMD=age-related macular degeneration; CI=confidence interval; FAF=fundus autofluorescence; GA=geographic atrophy; MMRM=mixed models for repeated measures.

*6-month time point was not part of the primary analysis, is observational in nature and should be interpreted with caution, and cannot be considered conclusive.

^†Percent difference is calculated by 100×(difference)/(least squares mean from sham).

IZERVAY is the only GA treatment to demonstrate statistically significant efficacy at one year in two Phase 3 trials^2,4

Dr. Khanani: The GATHER trials explained

Image of Dr. Arshad Khanani from the video "The GATHER trials explained"

Dr. Arshad Khanani walks us through the key findings from the GATHER1 and GATHER2 trials, highlighting IZERVAY’s statistically significant impact on slowing GA progression. He explains how the treatment effect not only begins as early as 6 months* but also continues to grow over time, more than doubling by 24 months.^2,5

Geographic atrophy, or GA, can progress quickly and unpredictably, and your patients are at risk of losing vision each day.¹ Taking action to potentially buy more time with their remaining vision matters to your patients.

In a survey of people with self-reported GA, 84% said they would try a treatment to slow GA and preserve their vision for longer, but only 14% receive treatment.^2,3 Preserving your patients' vision is more than just their sight, it's about potentially protecting how your patients' may visually experience life for longer.

Hi, I’m Arshad Khanani, Director of Clinical Research and Director of Fellowship at Sierra Eye Associates, and Clinical Professor at the University of Nevada, Reno School of Medicine. Today I want to talk to you about IZERVAY™ (avacincaptad pegol intravitreal solution): a tool that we can use to protect patients’ healthy retinal cells for longer by slowing down the progression of GA.

IZERVAY is indicated for the treatment of geographic atrophy secondary to age-related macular degeneration, or AMD.⁴ IZERVAY is contraindicated in patients with ocular or periocular infections and in patients with active intraocular inflammation.⁴ Please see additional safety information at the end of the video.

IZERVAY was studied in patients with GA due to AMD in two randomized, multicenter Phase 3 trials: GATHER1, over 18 months, and GATHER2, over 24 months, with 624 patients across both trials.^4-7 Both GATHER1 and GATHER2 were designed to evaluate the efficacy and safety of IZERVAY compared to sham with a primary endpoint at 12 months and additional long-term analyses conducted at 18 and 24 months.⁴

At the 12-month time point, IZERVAY achieved its primary clinical endpoints in both the GATHER1 and GATHER2 trials, demonstrating stat significant protection of healthy retinal cells within the first year of treatment with a 35% and 18% reduction in the annualized rate of GA growth in the GATHER trials.⁴ It is important to note that IZERVAY is the only GA treatment to demonstrate stat significant efficacy at one year in two Phase 3 trials.⁸ In addition to this early efficacy within the first year, IZERVAY started protecting healthy retinal cells as soon as 6 months. As you see through this 12-month timeframe, IZERVAY’s effect continued to grow in its separation from sham. This trend continued through 24 months.⁴ Let’s go there next.

When we look at the 24-month clinical data from GATHER2, IZERVAY demonstrated a 14% reduction in the annualized rate of GA growth with an increasing and doubling effect from baseline to 24 months compared to baseline to 12 months. At first glance, you may ask yourself how there could be a doubling effect when the results from GATHER2 year 1 showed an 18% annualized reduction in growth rate and GATHER2 across 24 months showed a 14% annualized reduction.^4,9 Let’s take a closer look.

In GATHER2, patients receiving monthly IZERVAY were re-randomized at Month 12 to either continue monthly dosing or transition to every-other-month dosing.⁴ This re-randomization created two distinct treatment subgroups within the active arm for the second year of the study. As a result, new slopes for each subgroup needed to be recalculated from baseline to 24 months. Because this calculation separates the data into two distinct dosing regimens, monthly or every-other-month, we need to look at each treatment group in comparison to itself. In conclusion, the addition of different subgroups make it difficult to compare Year 1 and Year 2 data, which is why an annualized rate was calculated.⁴

Additionally, when we look at the piecewise analysis, which helps us understand how the treatment effect varies across 6-month time periods, we observe that the treatment effect more than doubled over the full 24 months as compared to the first 12 months.⁹ What makes the 24-month data meaningful is that it demonstrated a cumulative and increasing treatment effect over time. We see in the data that the separation between IZERVAY treatment groups versus sham continued to widen beyond Month 12, indicating that the treatment effect not only persisted, it increased over time.⁵

Now let's take a look at IZERVAY’s safety profile as demonstrated in the GATHER trials. IZERVAY is the only FDA-approved GA treatment with no warning or precaution for intraocular inflammation or retinal vasculitis.^4,10 In the GATHER1 and GATHER2 trials, at 12 months, we saw a slight increase in neovascular wet AMD or choroidal neovascularization in patients treated with IZERVAY compared to the sham group. The rate was 7% in the IZERVAY treated group versus 4% in the sham group. In GATHER2, over 24 months, the rate of neovascular wet AMD or choroidal neovascularization was 12% with IZERVAY and 9% with sham.^4,9 Safety findings through 24 months in patients with GA secondary to AMD were consistent with those observed at 12 months.^5,6,9

We know that patients with GA will progress over time, but with IZERVAY, we have the potential to help our patients preserve their vision for longer.¹ IZERVAY is the only GA treatment to demonstrate stat significant efficacy at one year in two Phase 3 trials.^4,8 It also starts working early with efficacy demonstrated within the first year, and has continued to show an increasing treatment effect over time.^4,9

As a physician, I’m looking at the totality of the data, and that’s why IZERVAY is my choice for my patients with GA. It’s time to close that gap between the 84% of patients with GA who desire treatment and the 14% who actually receive it.

INDICATION

IZERVAY™ (avacincaptad pegol intravitreal solution) is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD)

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

IZERVAY is contraindicated in patients with ocular or periocular infections and in patients with active intraocular inflammation.

WARNINGS AND PRECAUTIONS

Endophthalmitis and Retinal Detachments

Intravitreal injections, including those with IZERVAY, may be associated with endophthalmitis and retinal detachments. Proper aseptic injection technique must always be used when administering IZERVAY in order 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.

Neovascular AMD

In clinical trials, use of IZERVAY was associated with increased rates of neovascular (wet) AMD or choroidal neovascularization (7% when administered monthly and 4% in the sham group) by Month 12. Over 24 months, the rate of neovascular (wet) AMD or choroidal neovascularization in the GATHER2 trial was 12% in the IZERVAY group and 9% in the sham group. Patients receiving IZERVAY should be monitored for signs of neovascular AMD.

Increase in Intraocular Pressure

Transient increases in intraocular pressure (IOP) may occur after any intravitreal injection, including with IZERVAY. Perfusion of the optic nerve head should be monitored following the injection and managed appropriately.

ADVERSE REACTIONS

Most common adverse reactions (incidence ≥5%) reported in patients receiving IZERVAY were conjunctival hemorrhage, increased IOP, blurred vision, and neovascular age-related macular degeneration.

Please see full Prescribing Information on IZERVAYecp.com.

References

1. Fleckenstein M, Mitchell P, Freund KB, et al. The progression of geographic atrophy secondary to age-related macular degeneration. Ophthalmology. 2018;125(3):369-390. 2. Bakri SJ, Brinkmann CK, Mulvey A, et al. Characterizing patient perceptions of living with geographic atrophy: the global Geographic Atrophy Insights Survey. Clin Ophthalmol. 2024;18:3725-3737. 3. Astellas Pharma US, Inc. Izervay. Data on File. 4. Izervay. Package insert. Northbrook, IL: Astellas Pharma US, Inc.; 2025. 5. Patel SS, Lally DR, Hsu J, et al. Avacincaptad pegol for geographic atrophy secondary to age-related macular degeneration: 18-month findings from the GATHER1 trial. Eye (Lond). 2023;37(17):3551-3557. 6. 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;402(10411):1449-1458. 7. Clinical Trials.gov. Zimura in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration. Accessed August 14, 2025. https://clinicaltrials.gov/study/NCT02686658 8. 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, randomized, double-masked, sham-controlled, phase 3 trials. Lancet. 2023;402(10411):1434-1448. 9. Astellas Pharma US, Inc. Izervay. Data on File. 10. Syfovre. Package Insert. Waltham, MA: Apellis Pharmaceuticals. 2025.

Post hoc US-only data

A post hoc analysis of the GATHER2 US-only patient population observed a 32% reduction in mean rate of GA growth⁵

MMRM analysis at 12 months vs sham in US subjects^‡

Graph of efficacy data from post hoc analysis of GATHER2 US-only patient population study: 32% reduction in mean rate of GA growth at 12 months

In a post hoc analysis of the international GATHER2 trial, the reduction in mean rate of growth (slope) in GA was analyzed over 12 months for patients receiving IZERVAY by geographic region (US vs rest of world). Data shown are for the 181 US-only patients, who accounted for 40% of the enrolled patients in GATHER2. These patients had a mean baseline lesion size that was 13% smaller than patients outside the US.^2,5

Given the exploratory post hoc nature of the data, these results should be interpreted with caution and cannot be considered conclusive

*6-month time point was not part of the primary analysis, is observational in nature and should be interpreted with caution, and cannot be considered conclusive.

^‡Post hoc analysis in mean rate of growth (slope) in GA area over 12 months for patients in the US included 89 and 92 patients treated with IZERVAY and sham, respectively.

^§Percent difference is calculated by 100×(difference)/(growth rate from sham).

We see throughout the data that IZERVAY starts working early within one year to reduce GA lesion growth and protect healthy retinal cells. Highlighted by the fact that it is the only GA treatment to demonstrate statistically significant efficacy at one year in two Phase 3 trials, IZERVAY has the potential to change the trajectory of GA for our patients.”^2,4

– Dr. Arshad M. Khanani, Vitreoretinal Surgeon

Hear more about efficacy data at 1 year from Dr. Khanani

Watch now

24-Month data

IZERVAY demonstrated an increasing treatment effect over 2 years²

GATHER2 was a 2-year, Phase 3, randomized, multicenter, double-masked, sham-controlled study evaluating the efficacy and safety of IZERVAY. In Year 2, patients receiving IZERVAY were re-randomized to receive IZERVAY monthly or every other month.⁵

Analysis of mean growth in GA area (mm²) at Month 24 vs sham^5||

Piecewise spline multivariate slope.

The annualized rate of GA growth (MMRM analysis)^¶ at 24 months in GATHER2

IZERVAY 2 mg EM²

2.23 mm²/year
14% reduction at 24 months; difference vs sham (95% Cl) mm²/year=0.36 (0.07-0.66); p=0.0165^#

The recommended dose for IZERVAY is 2 mg once monthly (approximately 28 ± 7 days)

EM=every month.

^||Analysis is based on MMRM assuming a piecewise linear trend at Month 6, 12, 18, including effects for treatment, time, and time by treatment interaction.

^¶Non-transformed GA growth slope analysis.

^#Percent difference is calculated by 100×(difference)/(least squares mean from sham).

See full trial design

What makes the 24-month data meaningful is that they capture a cumulative effect over time. We see in the data that the separation between IZERVAY and sham continued to widen beyond Month 12, indicating that the treatment effect not only persisted, it more than doubled.”⁵

– Dr. Arshad M. Khanani, Vitreoretinal Surgeon

Hear more about efficacy data at 2 years from Dr. Khanani

Watch now

Post hoc vision data

Vision loss analyses

Post hoc loss of driving vision analysis

In a post hoc analysis, fewer IZERVAY patients lost their driving eligibility compared to sham⁸

Driving vision threshold of 20/40 at or up to 12 months

In a pooled post hoc analysis of the GATHER trials, fewer patients on IZERVAY fell below the driving vision threshold of 20/40 at or up to 12 months compared to sham.⁸

The absolute low vision BCVA cutoff varies by state in the United States. The cutoff for loss of legal driving vision in this post hoc analysis was eyes with a baseline of ≥70 letters (20/40) that progressed to ≤60 letters (20/63) at or up to Month 12. Persistent loss of driving vision was defined as patients who progressed to ≤60 letters at 2 consecutive post-baseline visits.⁸

There are a number of factors that determine a patient's ability to drive and this decision should be considered carefully by each patient and their doctor
Given the exploratory post hoc nature of the data, these results should be interpreted with caution and cannot be considered conclusive

BCVA=best corrected visual acuity.

Trial design

IZERVAY was evaluated in patients with GA secondary to AMD²

Trial design

EOM=every other month.

**Patients continuing in the study through 24 months and originally randomized to the IZERVAY 2 mg arm at the outset of the study were re-randomized at Month 12 to either continue to receive IZERVAY EM (n=96) or receive IZERVAY EOM (n=93). Patients treated with sham in the first 12 months continued monthly sham treatment.

Trial design: The efficacy and safety of IZERVAY were demonstrated in 2 randomized, multicenter, double-masked, sham-controlled, 18-month and 24-month studies in patients with GA due to AMD. The primary endpoint evaluated the mean rate of GA growth (slope) from baseline to Month 12, measured by fundus autofluorescence (FAF) at 3 time points (baseline, Month 6, and Month 12). In GATHER2, the mean rate of GA growth (slope) measured by FAF was evaluated at 2 additional time points (Month 18 and Month 24).²

Case study

Case study of a GATHER2 clinical trial patient

This is the experience of a 79-year-old female with bilateral GA who reported good vision but said she needed a magnifying glass to read the newspaper

The patient was enrolled in the IZERVAY clinical trial for treatment of the right eye, and the left eye was observed. 2.5 years after initiating treatment in the right eye, product became available and the left eye was treated with IZERVAY.

Baseline vision was 20/40 OD and 20/63 OS
In the right eye, there was a 4.01-mm² nonsubfoveal GA patch
In the left eye, there was a 0.77-mm² patch of GA inferiorly
Hyperfluorescence at the lesion border signifies disease activity and is an indicator of progression

In this patient, IZERVAY slowed lesion growth over time

IZERVAY-treated
right eye (OD)

Untreated
left eye (OS)

Treatment initiated

IZERVAY-treated right eye (OD)

Image of right eye treated with IZERVAY and untreated left eye at treatment initiation

Untreated left eye (OS)

1y 1m

IZERVAY-treated right eye (OD)

Untreated left eye (OS)

2y 11m

IZERVAY-treated right eye (OD)

Left eye (OS) treated with IZERVAY at 2.5 years

Hear more about this patient case from Dr. David Eichenbaum

Hi, I’m Dr. David Eichenbaum, and I am Director of Research at Retina Vitreous Associates of Florida. The tool I’m talking about today is IZERVAY (avacincaptad pegol intravitreal solution).^1-3 IZERVAY is for the treatment of geographic atrophy (GA), secondary to age-related macular degeneration (AMD), and is contraindicated in patients with ocular or periocular infections and in patients with active intraocular inflammation.² Please watch the full video for additional important safety information.

I’ve been a protector of my patients’ vision for 17 years and counting. One area I’m particularly passionate about is geographic atrophy, or GA. GA progression is not linear—it can progress unpredictably over time, and now we have tools that are proven to slow GA progression, which may help preserve vision longer by protecting remaining healthy retinal cells.^1-3

Now, let me show you a patient case from my colleague, Dr. Beth Richter, where starting treatment with IZERVAY had a clear impact on the patient’s GA progression and outcomes over the course of almost 3 years.

As you’ll see, in this 79-year-old patient with bilateral GA, vision was preserved in the IZERVAY-treated eye for 3 years, while the untreated eye lost 8 lines of vision—resulting in catastrophic vision loss.

Let’s jump in: this patient reported good vision but had started using a magnifying glass to read the newspaper. Her baseline vision was 20/40 in her right eye and 20/63 in her left. In her baseline FAF images, her right eye displayed a 4-mm² non-subfoveal GA patch, less than 500 µm from the foveal center. The left eye displayed a 0.77-mm² GA patch and was more than 500 µm from the foveal center. The hyperautofluorescence at the lesion border signified disease activity and was an indicator of GA progression.¹

At the time of her diagnosis, IZERVAY was not yet approved. Therefore, the patient enrolled in the IZERVAY clinical trial for the treatment of the right eye, and the left eye was just observed. Approximately one year after presentation and starting monthly treatment in the right eye, her vision had decreased from 20/40 to 20/50 in the right eye and from 20/63 to 20/80 in the untreated left eye.

Two years after her initial presentation, the right eye was receiving monthly IZERVAY treatment and had minimal progression, while the untreated left eye showed significant progression and decrease in visual acuity.

Once IZERVAY was FDA-approved, treatment was started in the left eye. Vision at the start of treatment in the left eye was 20/400. During the period prior to IZERVAY treatment, the left eye went from 20/63 to 20/400, a catastrophic loss of vision. After 4 months of IZERVAY treatment, visual acuity had changed to 20/500. Meanwhile, visual acuity remained relatively stable at 20/50 in the right eye.

This is a great example of how treating patients with GA gives them the best chance to preserve their vision for longer—a treatment goal that is valued by 84% of patients with GA.⁴ We know GA will progress in every patient, and to protect the healthy retinal cells that remain for longer, we need to start treating GA as early as possible.¹

INDICATION

IZERVAY™ (avacincaptad pegol intravitreal solution) is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD)

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

IZERVAY is contraindicated in patients with ocular or periocular infections and in patients with active intraocular inflammation.

WARNINGS AND PRECAUTIONS

Endophthalmitis and Retinal Detachments

Intravitreal injections, including those with IZERVAY, may be associated with endophthalmitis and retinal detachments. Proper aseptic injection technique must always be used when administering IZERVAY in order 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.

Neovascular AMD

In clinical trials, use of IZERVAY was associated with increased rates of neovascular (wet) AMD or choroidal neovascularization (7% when administered monthly and 4% in the sham group) by Month 12. Over 24 months, the rate of neovascular (wet) AMD or choroidal neovascularization in the GATHER2 trial was 12% in the IZERVAY group and 9% in the sham group. Patients receiving IZERVAY should be monitored for signs of neovascular AMD.

Increase in Intraocular Pressure

Transient increases in intraocular pressure (IOP) may occur after any intravitreal injection, including with IZERVAY. Perfusion of the optic nerve head should be monitored following the injection and managed appropriately.

ADVERSE REACTIONS

Most common adverse reactions (incidence ≥5%) reported in patients receiving IZERVAY were conjunctival hemorrhage, increased IOP, blurred vision, and neovascular age-related macular degeneration.

Please see full Prescribing Information on IZERVAYecp.com.

References

1. Fleckenstein M, Mitchell P, Freund KB, et al. The progression of geographic atrophy secondary to age-related macular degeneration. Ophthalmology. 2018;125(3):369-390. 2. Izervay. Package insert. Northbrook, IL: Astellas Pharma US, Inc.; 2025. 3. 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;402(10411):1449-1458. 4. Bakri SJ, Brinkmann CK, Mulvey A, et al. Characterizing patient perceptions of living with geographic atrophy: the global Geographic Atrophy Insights Survey. Clin Ophthalmol. 2024;18:3725-3737.

OD=oculus dexter; OS=oculus sinister.
Images courtesy of Dr. Beth Richter.
This is an individual patient case study. It should be interpreted with caution and cannot be considered conclusive. Individual results may vary. In the GATHER trials, sham was used as the comparator.

IZERVAY provided significant protection of healthy retinal cells in just one year of treatment2

IZERVAY reduced the annualized rate of GA lesion growth in two Phase 3 trials2

Reductions in mean rate of growth (MMRM analysis) at 12 months vs sham2

IZERVAY is the only GA treatment to demonstrate statistically significant efficacy at one year in two Phase 3 trials2,4

Dr. Khanani: The GATHER trials explained

A post hoc analysis of the GATHER2 US-only patient population observed a 32% reduction in mean rate of GA growth5

MMRM analysis at 12 months vs sham in US subjects‡

IZERVAY demonstrated an increasing treatment effect over 2 years2

Analysis of mean growth in GA area (mm2) at Month 24 vs sham5||

The annualized rate of GA growth (MMRM analysis)¶ at 24 months in GATHER2

What makes the 24-month data meaningful is that they capture a cumulative effect over time. We see in the data that the separation between IZERVAY and sham continued to widen beyond Month 12, indicating that the treatment effect not only persisted, it more than doubled.”5

Vision loss analyses

In a post hoc analysis, fewer IZERVAY patients lost their driving eligibility compared to sham8

Driving vision threshold of 20/40 at or up to 12 months

IZERVAY was evaluated in patients with GA secondary to AMD2

Case study of a GATHER2 clinical trial patient

This is the experience of a 79-year-old female with bilateral GA who reported good vision but said she needed a magnifying glass to read the newspaper

In this patient, IZERVAY slowed lesion growth over time

Hear more about this patient case from Dr. David Eichenbaum

See safety data

IZERVAY provided significant protection of healthy retinal cells in just one year of treatment²

IZERVAY reduced the annualized rate of GA lesion growth in two Phase 3 trials²

Reductions in mean rate of growth (MMRM analysis) at 12 months vs sham²

IZERVAY is the only GA treatment to demonstrate statistically significant efficacy at one year in two Phase 3 trials^2,4

A post hoc analysis of the GATHER2 US-only patient population observed a 32% reduction in mean rate of GA growth⁵

MMRM analysis at 12 months vs sham in US subjects^‡

IZERVAY demonstrated an increasing treatment effect over 2 years²

Analysis of mean growth in GA area (mm²) at Month 24 vs sham^5||

The annualized rate of GA growth (MMRM analysis)^¶ at 24 months in GATHER2

What makes the 24-month data meaningful is that they capture a cumulative effect over time. We see in the data that the separation between IZERVAY and sham continued to widen beyond Month 12, indicating that the treatment effect not only persisted, it more than doubled.”⁵

In a post hoc analysis, fewer IZERVAY patients lost their driving eligibility compared to sham⁸

IZERVAY was evaluated in patients with GA secondary to AMD²