Does ACP reduce loss of driving vision?

GATHER1 and GATHER2 evaluated the safety and efficacy of ACP in patients with GA secondary to age-related macular degeneration (AMD).^3,4

• Patients had BCVA of 25-80 early treatment diabetic retinopathy study letters in the study eye at baseline.
• Post-hoc analyses assessed the loss of BCVA to levels below driving thresholds in patients eligible to drive at baseline.

Two separate sub-analyses were conducted with different methodological approaches:

Danzig et al. sub-analysis:¹

• In a subset, the proportion of study eyes with BCVA loss below the driving eligibility threshold at Month 12 among those eligible to drive at baseline was assessed.
• Evaluated two cutoffs:
  • Baseline ≥ 70 letters (≥ 20/40) with worsening to ≤ 60 letters (≤ 20/63) at Month 12 visit and at 2 consecutive post-baseline visits.
  • Baseline ≥ 75 letters (≥ 20/32) with worsening to ≤ 65 letters (≤ 20/50) at Month 12 and at 2 consecutive post-baseline visits.
• Persistent loss of driving vision was defined as BCVA below threshold at two consecutive postbaseline visits.
• ACP 2 mg was associated with a lower proportion of patients with loss of BCVA to a level below the driving eligibility threshold compared with sham over Year 1 (Figure 1).
• Among patients with a baseline of ≥ 70 letters:
  • 3.1% of patients treated with ACP 2 mg had a BCVA of ≤ 60 letters at Year 1 compared with 7.3% of patients treated with sham, resulting in a relative risk reduction of 57.5%.
  • 8.7% of patients treated with ACP 2 mg demonstrated persistent loss of driving vision at Year 1 compared with 13.6% of patients treated with sham, resulting in a relative risk reduction of 36.0%.
• Among patients with a baseline of ≥ 75 letters:
  • 4.7% of patients treated with ACP 2 mg had a BCVA of ≤ 65 letters at Year 1 compared with 10.4% of patients treated with sham, resulting in a relative risk reduction of 54.8%.
  • 4.7% of patients treated with ACP 2 mg demonstrated persistent loss of driving vision at Year 1 compared with 9.6% of patients treated with sham, resulting in a relative risk reduction of 51.0%.

Figure 1. Proportion of patients with BCVA loss below driving eligibility threshold¹

Chang et al. subanalysis:²

• Time-to-event analysis assessed the impact of ACP 2 mg, administered EM or EOM, on the risk of progressing to loss of driving eligibility over 24 months.
• Analysis was performed in patients eligible to drive at baseline (BCVA ≥ 70 early treatment diabetic retinopathy study (ETDRS) letters in the study eye); loss of driving eligibility was defined as BCVA ≤ 60 letters at 2 consecutive post-baseline visits over 24 months.
• Among patients with a baseline BCVA of ≥ 70 letters (n = 403), mean BCVA was similar between ACP 2 mg (n = 188) and sham groups (n = 215) at baseline.
• Patients receiving ACP 2 mg EM or EOM compared to sham:
  • The risk probability of progressing to loss of driving eligibility in the study eye at 24 months was 12.6% for ACP 2 mg EM or EOM vs 20.1% for sham, a 41% relative risk reduction (Figure 2).
• Patients receiving ACP 2 mg EM only compared to sham:
  • The risk probability of progressing to loss of driving eligibility in the study eye at 24 months was 15.1% for ACP 2 mg EM only vs 20.1% for sham, a 35% relative risk reduction (Figure 3).

Figure 2. Risk of progressing to loss of driving eligibility^a over 24 months in patients with baseline BCVA ≥ 70 ETDRS letters treated with ACP 2 mg EM or EOM compared with sham²

Figure 3. Risk of progressing to loss of driving eligibility^a over 24 months in patients with baseline BCVA ≥ 70 ETDRS letters treated with ACP 2 mg EM only compared with sham ²

1. Danzig CJ, Khanani AM, Kaiser PK, et al. Vision Loss Reduction with Avacincaptad Pegol for Geographic Atrophy A 12-Month Post Hoc Analysis of the GATHER1 and GATHER2 Trials. Ophthalmol. Retin. 2024;8(11):1052-1060. Available at: https://doi.org/10.1016/j.oret.2024.04.023.

2. Chang M. Time-to-event analysis of driving eligibility maintenance following treatment with avacincaptad pegol in patients with geographic atrophy [poster]. Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) 2026.

3. Jaffe GJ, Westby K, Csaky KG, et al. C5 Inhibitor Avacincaptad Pegol for Geographic Atrophy Due to Age-Related Macular Degeneration A Randomized Pivotal Phase 2/3 Trial. Ophthalmology. 2021;128(4):576-586. Available at: https://doi.org/10.1016/j.ophtha.2020.08.027.

4. 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.