Avacincaptad pegol slows GA growth through 3.5 years in GATHER2 OLE

According to a poster presented at the 2026 Optometry’s Meeting of the American Optometric Association, held from June 17-20, in Phoenix, Arizona, avacincaptad pegol 2 mg (Izervay; Astellas) demonstrated increasing benefit over time in slowing geographic atrophy (GA) lesion growth through 3.5 years of follow-up in the GATHER2 open-label extension study, with both continuously treated patients and those switched from sham showing significant reductions in lesion growth compared with projected sham.¹

The data, presented by Mary Beth Yackey, OD, of Cincinnati Eye Institute, represent the longest available dataset for an approved complement C5 inhibitor in GA. For optometrists managing patients with AMD in comanagement with retinal specialists, the GATHER2 OLE findings are directly relevant to counseling conversations about long-term treatment commitment, providing perhaps the clearest picture yet of how treatment timing and duration interact with outcomes in GA, a disease for which the OD’s role in initiating discussion, monitoring progression, and supporting adherence is substantial.

GATHER2 OLE design and primary GA lesion growth results at 42 months

The GATHER2 OLE (NCT05536297) enrolled 278 patients who completed the phase 3 GATHER2 trial through month 24 and subsequently received avacincaptad pegol 2 mg every month (EM) for an additional 18 months.¹ Three groups were analyzed: patients who received avacincaptad pegol continuously throughout GATHER2 and the OLE (ACP to ACP EM, n = 96), patients who had been randomized to sham in GATHER2 and switched to active treatment in the OLE (Sham to ACP EM, n = 153), and a projected sham group modeled from the GATHER2 control arm.

In the ACP to ACP group, avacincaptad pegol reduced GA lesion growth by 28.8% compared with the projected sham over 42 months (P <.001). Continuously treated patients had 1.83 mm² of retina area protected compared with sham and projected sham over 42 months.

Among patients originally assigned to sham who switched to active treatment at month 24, GA lesion growth was reduced by 37.1% compared to projected sham from months 24 to 42 (P <.001), and by 40.5% compared with projected sham from months 24 to 42 (P <.001), indicating a meaningful benefit even after delayed initiation.¹ Patients who switched from sham had 0.73 mm² of retina area protected over 42 months following treatment initiation.

Retinal protection, early treatment benefit, and 3.5-year safety profile of avacincaptad pegol

The OLE results add a critical dimension to the existing GATHER evidence base: benefit increased over time with continued treatment, and early initiation conferred greater cumulative retinal protection.¹ The 1.83 mm² area of retinal preservation in continuously treated patients compared with 0.73 mm² in those who switched from sham at month 24 illustrates the compounding advantage of earlier treatment. For ODs who are following patients with intermediate AMD or early GA, these findings support prompt discussion of anticomplement therapy and timely referral to retinal specialists before lesions progress substantially.

The 18-month OLE safety profile was consistent with the GATHER2 pivotal trial, with no new safety signals identified.¹ Ocular treatment-emergent adverse events occurring in at least 2% of study eyes included IOP increase, cataract, conjunctival hemorrhage, vitreous detachment, and reduced visual acuity. One case of endophthalmitis occurred in the sham to ACP group (0.7%).

Intraocular inflammation was identified in 5 cases across 4,203 total injections (0.1%), all of which were anterior, and none were serious or related; no cases recurred. No cases of retinal vasculitis or occlusive vasculitis were reported during the OLE, addressing a class-level safety concern across complement inhibitors.¹ New-onset choroidal neovascularization was observed in 7 of 125 eyes (5.6%) in the ACP to ACP group and 14 of 151 eyes (9.3%) in the sham to ACP group.

Yackey and colleagues noted the findings support the conclusion that avacincaptad pegol demonstrated increasing benefit in slowing GA lesion growth with continued use and showed greater efficacy with earlier treatment initiation.¹

Optometrists monitoring patients receiving avacincaptad pegol injections can reference the OLE safety profile when preparing patients for treatment, particularly regarding the low rates of intraocular inflammation and the absence of retinal vasculitis signals through 3.5 years.¹ The data also inform the patient conversation when delayed initiation is under discussion, reinforcing the value of earlier over later referral for eligible patients with GA.

References

1. Yackey MB, presenting on behalf of Khanani AM, Heier JS, et al. Avacincaptad pegol for geographic atrophy: 3.5-year results from the GATHER2 open-label extension trial. Poster presented at: AOA 2026; June 17–20; Phoenix, AZ. Poster #8.

2. Khanani AM, Patel SS, Staurenghi G, et al. Efficacy and safety of avacincaptad pegol in patients with geographic atrophy: GATHER2 12-month results. Ophthalmology. 2023;130(6):648-656. doi:10.1016/j.ophtha.2023.02.020