A recent study sponsored by Astellas Pharma Inc. evaluated real-world avacincaptad pegol (ACP)—known as IZERVAY—treatment patterns in patients with age-related macular degeneration (AMD) receiving concomitant anti-vascular endothelial growth factor (VEGF) treatment.
These findings were presented at the American Society of Retinal Specialists (ASRS) 2026 meeting in Montréal, Canada.
Let’s start with some background on IZERVAY.
ACP 2 mg (IZERVAY, Astellas Pharma) is a C5 complement inhibitor approved by the FDA in August 2023 for the treatment of geographic atrophy (GA) secondary to AMD.
This approval was based on two phase 3 pivotal clinical trials:
- GATHER1 (NCT02686658): Patients received IZERVAY every month (EM) or sham for 18 months
- GATHER2 (NCT04435366): Patients were given IZERVAY EM or sham for 12 months, after which they were re-randomized to IZERVAY EM or every-other-month (EOM) for up to 24 months
Note: Patients with existing choroidal neovascularization (CNV) were excluded from the GATHER1 and GATHER2 clinical trials; however, patients who acquired CNV in GATHER2 remained in the study and underwent anti-VEGF treatment.
Now bring in anti-VEGF therapy.
To start: GA and wet AMD can coexist in the same eye. In fact, studies have found an increased rate of conversion to wet AMD associated with complement inhibitors—and as such, some patients may need to be treated for both conditions.
However: There is a dearth of information about the patient characteristics, treatment patterns, and adverse event (AE) profiles for patients who are routinely treated with ACP 2 mg and concomitant anti-VEGF therapy.
Didn’t I recently hear about IZERVAY?
Indeed. Just this past May, Astellas announced results from a post-hoc analysis of the phase 3 clinical trials of IZERVAY evaluating its impact on the risk of progressing to loss of driving eligibility in patients with GA secondary to AMD.
One of the key findings: At 24 months, the risk of progressing to loss of driving eligibility was 12.6% for IZERVAY EM or EOM compared to 20.1% for sham—representing a 41% relative risk reduction for IZERVAY.
Let’s move on to this new study.
In this observational study, investigators utilized the American Academy of Ophthalmology (AAO) IRIS Registry (Intelligent Research In Sight) to analyze ACP treatment patterns and safety outcomes in patients with GA and wet AMD receiving ACP 2mg and concomitant anti-VEGF treatment in the United States.
The cohort: 10,181 patients (13,391 eyes) aged ≥50 years who received their first (index) ACP 2-mg injection between September 1, 2023 and August 31, 2024.
What else should we know about it?
Additional details:
- Diagnosis of GA in the eye that received the ACP injection must have occurred on or before the index date
- Patients with ≤30 days of follow-up data available after their index data were excluded from the study
- AEs were identified using diagnosis codes captured in the IRIS Registry during follow-up.
- Each ACP injection was evaluated for key AEs and vision loss documented between 1 and 30 days after ACP injection
Findings?
Of the 13,391 patient-eyes included, 3,045 (22.7%) received concomitant anti-VEGF treatment during follow-up period with ACP 2 mg, with the majority receiving anti-VEGF treatment prior to receiving ACP (n=2719, 89.3%).
- The mean follow-up: 24.6 weeks
Moreover: Of the patient-eyes receiving concomitant anti-VEGF treatment, 2,390 (78.5%) received anti-VEGF in the same eye as ACP either on the same day or within 60 days prior.
Tell me more.
The mean interval between ACP injections was similar in patient-eyes with and without concomitant anti-VEGF (7.2 vs. 6.9 weeks, respectively).
Most patient-eyes (n=2,615, 85.9%) with concomitant anti-VEGF treatment received two or more ACP injections during the follow-up, with a mean of 3.9 injections per patient-eye.
Concomitant anti-VEGF treatment was provided more than once in 1,976 (64.9%) patient-eyes, with a mean interval of 13.2 weeks between doses.
How many patients switched away from or quit IZERVAY?
The discontinuation rate for ACP treatment was slightly higher in patient-eyes with concomitant anti-VEGF treatment than in those without (10.8% vs. 6.7%, respectively).
The rate of switching to pegcetacoplan was low and similar between groups (2.5% vs. 3.4% for patient-eyes with and without concomitant anti-VEGF use, respectively).
And the reasoning behind this?
In the ASRS presentation, Deepak Sambhara, MD, FASRS of Eye Clinic of Wisconsin noted that some of the reasons for discontinuation or switching potentially include:
- Comorbidities
- Travel burden
- Burden of injections
- Prioritizing treating wet AMD rather than GA due to sudden vision impairment associated with the former
What about AEs?
Less than 4% of patient-eyes receiving concomitant anti-VEGF experienced treatment-emergent AEs, with 134 AEs per 10,000 ACP 2 mg injections reported with concomitant anti-VEGF and 93 AEs per 10,000 ACP 2 mg injections reported without concomitant anti-VEGF.
Key AEs included:
- CNV
- Wet AMD
- Intraocular inflammation
- Retinal vascular occlusion
- Endophthalmitis
- Retinal detachment
Tell me more.
Among eyes with concomitant anti-VEGF, CNV and nAMD were the most common key AEs, occurring in 1.5% and 1.3% of patient-eyes, respectively, consistent with the underlying disease process requiring anti-VEGF therapy.
Note: There may have been some overlap in the reporting of AEs as CNV and wet AMD share some International Classification of Diseases, Tenth Revision (ICD-10) codes.
Any limitations to consider?
Definitely a few to keep in mind when interpreting the findings:
- The study’s limited timeframe
- Data was based on medical records dependent on documentation and may be incomplete or impacted by common workflows
- Due to the FDA approval of ACP 2 mg in 2023 for GA, the mean follow-up period was ~6 months
- As imaging data is not available in the IRIS Registry database, efficacy of ACP 2 mg was not examined in this real-world population
- Anti-VEGF injections recorded in the dataset were not confirmed to be administered for wet AMD, and the efficacy and safety of anti-VEGF was not evaluated
And lastly: the take home.
Overall, this real-world study using the IRIS Registry data demonstrated that concomitant anti-VEGF use can be incorporated with ACP 2 mg without substantial effect on ACP treatment patterns, while maintaining an expected safety profile.
- And while concomitant anti-VEGF use was associated with a slightly higher number of key AEs, the overall rate of AEs was low.
As such: Longer follow-up may further characterize long-term outcomes with concomitant anti-VEGF treatment.