Intravitreal complement inhibitor treatment for GA viewed favorably by patients

A new British study reported that treatment with intravitreal complement inhibitors (IVCIs) for geographic atrophy (GA) was viewed favorably by patients if the treatment was thought to impart visual benefits,¹ according to first author Christiana Dinah, BSc, MBBS, MRes, and colleagues. The findings were published in JAMA Ophthalmology.

Dr Dinah is from the Ophthalmology Department, Central Middlesex Hospital, London North West University Healthcare National Health Service Trust, and the Department of Brain Sciences, Imperial College London, both in London.

The United States Food and Drug Administration recently approved two IVCIs, pegcetacoplan (SYFOVRE, Apellis Pharmaceuticals) and avacincaptad pegol (Izervay, Astellas Pharma) for treating GA. “These treatments have been shown to slow down the anatomic progression of GA lesions.^2,3 Unfortunately, no functional benefit was demonstrated in the prespecified analysis by 24 months. Furthermore, complement inhibitor treatments for GA may be associated with a 2- to 4-fold increased risk of neovascular age-related macular degeneration (AMD) in the treated eye compared to sham,⁴” the investigators commented.

However, while the safety and efficacy of the drugs have been studied, “there has been limited focus on the perspectives of individuals with GA,” the investigators said. They cited their mixed-methods pilot study of 30 patients⁵ that investigated the opinions of UK patients with GA on the hypothetical acceptability of new intravitreal treatments. The study suggested that the undefined benefits for functional vision and fear of developing neovascular AMD were considerable concerns, Dr Dinah and colleagues explained. The patients also expressed concerns about the need for regular hospital visits, although more than half found regular treatments acceptable.

Regarding the pilot study,⁵ the authors commented, “The main factor motivating acceptability in this pilot study was the high priority placed on the continuation of vision-specific activities, particularly for participants with worse self-reported health. While participants understood that functional benefit had not been demonstrated, they felt the reduction in anatomic growth of GA lesions would inevitably translate to the preservation of functional vision for longer.”

What are patient attitudes toward IVCI?

The study goal was to quantify the acceptability of IVCI therapy to patients with GA in the UK, assuming vision outcome benefits are expected.

The study, which included 153 patients (60% women; mean age, 82 years) with GA in at least one eye, was carried out in nine UK National Health Service centres from April 2023 to April 2024; 38% of patients had GA in both eyes.

The investigators reported that the respective median corrected visual acuities with habitual correction in the better-seeing eye and in eyes where neither eye was better or worse were logMAR, 0.30 (approximate Snellen equivalent, 20/40) and 0.47 (approximate Snellen equivalent, 20/63).

“Among the 153 participants, 81 (53%; 95% CI, 45-61) reported IVCIs were very much or extremely acceptable under the theoretical scenarios provided. The proportion of patients finding IVCIs acceptable rose to 82% (95% confidence interval [CI], 76-88) when including those who rated prospective treatment as moderately acceptable. Belief in the perceived effectiveness of the treatment (ρ, 0.52; 95% CI, 0.40-0.63; P < 0 .001) and confidence in their ability to attend the eye clinic regularly (ρ, 0.51; 95% CI, 0.38-0.62; P < 0.001) correlated with overall acceptability,” Dr Dinah and colleagues reported.

The study showed that up to “82% of UK-based patients with GA could find IVCI therapy acceptable under the assumption that the therapy results in functional vision benefits.” This is despite prior research which demonstrates only an anatomic benefit has been found for these drugs, while visual acuity, reading speed and vision-related quality of life outcomes were not superior in treatment compared with sham groups.

The authors concluded by saying that “perception of functional benefit is key to patient acceptability when making decisions regarding IVCI therapy and highlight an urgent need for further research into functional phenotypes of GA and development of robust functional endpoints of clinical relevance to patients with GA. In health systems where IVCI or other emerging GA treatments become available for clinical use, a shared decision-making process that foregrounds patients’ unique preferences and circumstances remains essential.”

References

1. Dinah C, Enoch J, Ghulakhszian A, et al. Patient-reported importance of functional benefit in geographic atrophy. JAMA Ophthalmol. 2025; published online September 25; doi: 10.1001/jamaophthalmol.2025.3264

2. 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;402:1449-1458. doi:10.1016/S0140-6736(23)01583-0

3. 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;402:1434-1448. doi:10.1016/S0140-6736(23)01520-9

4. Tzoumas N, Riding G, Williams MA, Steel DHW. Complement inhibitors for age-related macular degeneration. Cochrane Database Syst Rev. 2023;6:CD009300. doi:10.1002/14651858.CD009300.pub3

5. Enoch J, Ghulakhszian A, Sekhon M, et al. Exploring patient acceptability of emerging intravitreal therapies for geographic atrophy: a mixed-methods study. Eye (Lond). 2023;37:3634-3642. doi:10.1038/s41433-023-02571-3