Can ACP be combined with anti-VEGF therapies in GA patients?

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Prescribing Information including BOXED WARNING

ACP was co-administered with anti-VEGF in patients who developed MNV, with no safety concerns.

In patients who developed macular neovascularization (MNV) in the study eye, co-administration of ranibizumab or aflibercept (anti-vascular endothelial growth factor (VEGF) therapies) with ACP (avacincaptad pegol) in the GATHER2 trial did not appear to negatively impact efficacy, and no new safety concerns were identified.^1–3
In a real-world study, patients who developed MNV and underwent anti-VEGF therapy during ACP treatment for geographic atrophy (GA) did not show significant visual improvement from the time of MNV diagnosis to the final assessment of visual acuity at 12 months.⁴

GATHER2 trial data:

GATHER2 was a randomized, double-masked, sham-controlled Phase 3 study that evaluated ACP 2 mg compared with sham in patients with non-center point involving GA secondary to age-related macular degeneration (AMD).^1,2

A case of suspected development of MNV in the study eye reported by the principal investigator, resulted in full imaging workup by the Duke Reading Center within one hour of submission. If diagnosed, eyes were treated with ranibizumab or aflibercept and patients remained in the study.
In the 2-year data readout of the GATHER 2 trial, the incidence of MNV in the study eye was 11.6% (26/225) in the ACP 2 mg group and 9.0% (20/222) in the sham control group.³
A post hoc sub-analysis of data was performed in patients with GA who developed and received treatment for MNV in the GATHER2 trial.¹
The incidence of ocular TEAEs in the study eye in patients who developed MNV was similar to that of those who did not develop MNV. In patients with GA who developed MNV and continued ACP treatment with concurrent anti-VEGF therapy, no new safety concerns were identified.
Anti-VEGF drug that was utilized in the study was according to the investigator’s discretion.
The concurrent administration of ACP with anti-VEGF did not appear to negatively impact the decline in GA growth in patients with MNV (Table 1).

Table 1. GA growth in patients without MNV vs. MNV conversion patients¹

ACP 2 mg GA
Growth Slope
(mm²)

Sham GA
Growth Slope
(mm²)

Difference

(Sham – ACP)

Analyses Method

Overall population

1.745
(N = 225)

2.121
(N = 222)

0.376

Mixed model (primary analyses in SAP)

MNV conversion patients

1.659
(n = 15)

2.059
(n = 9)

0.400

Simple summary of regression

SAP: statistical analysis plan

Real-world Evidence:

Rush et al conducted a case-controlled, retrospective study on patients with GA undergoing treatment with ACP (N = 56).⁴

Patients were divided into two equal cohorts (n = 28): patients who developed MNV and were treated with anti-VEGF therapy, and a control group who were complication-free.
The baseline characteristics of both cohorts did not show any significant differences.
At 12 months the MNV group had a greater reduction in visual acuity (−0.22 logMAR [−0.27 to −0.17] versus −0.06 logMAR [−0.12 to 0.00]; p = 0.0001), and an increase in GA total lesion size (1.78 mm² [1.53–2.03] versus 0.78 mm² [0.54–1.02]; p = 0.0001) compared to the control group (Table 2).

Table 2. 12 months outcome for study and control cohorts⁴

Variable	MNV group N = 28	Control group N = 28	P value
Mean number of ACP injections administered during the study period	8.9 (7.9–9.9)	9.5 (8.4–10.6)	0.79
VA at 12 months (logMAR)	0.54 (0.42–0.66)	0.43 (0.28–0.58)	0.07
Change in VA from baseline to 12 months (logMAR)	−0.22 (−0.27 to −0.17)	−0.06 (−0.12 to 0.00)	< 0.0001
Size of GA lesion at 12 months (mm²)	7.58 (5.58–9.58)	6.98 (5.48–8.48)	0.54
Change in size of GA lesion (mm²)	1.78 (1.53–2.03)	0.78 (0.54–1.02)	< 0.0001
Central macular thickness on OCT (microns)	250.7 (240.5–260.9)	245.1 (234.9–255.4)	0.56

VA: visual acuity; OCT: optical coherence tomography; logMAR: logarithm of the minimum angle of resolution

D’Souza D, Gibson A, Tang J, Desai D. The Safety of Avacincaptad Pegol in Combination With Anti-Vascular Endothelial Growth Factor Treatment in Patients With Wet Age-Related Macular Degeneration [poster]. AMCP Nexus 2023. Orlando, FL, USA. 2023.
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. Available at: https://doi.org/10.1016/s0140-6736(23)01583-0.
Khanani AM, Danzig CJ, Heier JS, et al. Avacincaptad pegol for geographic atrophy secondary to age-related macular degeneration: 2-year efficacy and safety results from the GATHER2 phase 3 trial. Ophthalmology. 2025;epub ahead of print. Available at: https://doi.org/10.1016/j.ophtha.2025.12.011.
Rush RB, Klein W, Rush SW, Reinauer R. One-Year Outcomes in Subjects Developing Macular Neovascularization While Undergoing Avacincaptad Pegol Therapy for Geographic Atrophy. Clin. Ophthalmol. 2025;19(0):111-118. Available at: https://doi.org/10.2147/opth.s498985.