Does ACP reduce loss of driving vision?

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ACP 2 mg reduced the progression to driving ineligibility compared with sham, particularly when BCVA is ≥ 75 letters.

A lower proportion of ACP-treated eyes treated with ACP 2 mg progressed to driving ineligibility over 12 months when compared with sham.¹ Pooled 24-month data suggest patients with geographic atrophy (GA) receiving ACP 2 mg may be less likely than those receiving sham to progress to driving restrictions or lose driving eligibility if they are treated when best corrected visual acuity (BCVA) is ≥ 75 letters.²

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).

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

“Loss” defined as BCVA of ≤ 60 letters (cutoff 1) or ≤ 65 letters (cutoff 2) at Month 12 (left graphs).

“Persistent loss” defined as BCVA of ≤ 60 letters (cutoff 1) or ≤ 65 letters (cutoff 2) at two consecutive postbaseline visits (right graphs).

Adapted from: Danzig CJ, Ophthalmol Retina, 2024.

Hariprasad et al. subanalysis:²

A post-hoc analysis evaluated the proportion of patients with loss or persistent loss of BCVA to a level below the driving eligibility threshold at any post baseline visit or at any two consecutive visits, respectively, up to 12 months and up to 24 months (Figure 2).

Figure 2. Definitions of driving eligibility.

Adapted from: Hariprasad SM, American Society of Retina Specialists (ASRS), 2024.

ACP 2 mg was associated with a lower proportion of patients with loss and persistent loss of BCVA to a level below the driving eligibility threshold compared with sham up to 12 months (Figure 3).

Figure 3. Proportion of patients with BCVA loss below driving eligibility threshold up to 12 months^a^,²

Left graph comparisons: Loss, p = 0.0947; persistent loss, p = 0.1608. Right graph comparisons: Loss, p = 0.3463; persistent loss, p = 0.1531.

^a“Loss” defined as BCVA of ≤ 65 letters (left graph) or ≤ 60 letters (right graph) at any postbaseline visit.

^b“Persistent loss” defined as BCVA of ≤ 65 letters (left graph) or ≤ 60 letters (right graph) at two consecutive postbaseline visits.

Adapted from: Hariprasad SM, ASRS, 2024.

ACP 2 mg was associated with a lower proportion of patients with persistent loss of BCVA to a level below the driving eligibility threshold compared with sham up to 24 months (Figure 4).

Figure 4. Proportion of patients with BCVA loss below driving eligibility threshold up to 24 months^a^,²

Left graph comparisons: Loss, p = 0.0947; persistent loss, p = 0.0726. Right graph comparisons: Loss, p = 0.8162; persistent loss, p = 0.3473.

^aThere was no change in the proportion of patients with “loss of driving eligibility” in the baseline BCVA of ≥ 70 letters group.

^b“Loss” defined as BCVA of ≤ 65 letters (left graph) or ≤ 60 letters (right graph) at any postbaseline visit.

^c“Persistent loss” defined as BCVA of ≤ 65 letters (left graph) or ≤ 60 letters (right graph) at two consecutive postbaseline visits.

Adapted from: Hariprasad SM, ASRS, 2024.

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.
Hariprasad SM, Khanani AM, Kiernan DF, et al. Maintenance of driving ability in patients with geographic atrophy from GATHER1 and GATHER2 clinical trials: a post hoc analysis [oral slide presentation]. American Society of Retina Specialists. Stockholm, Sweden. 2024.
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.
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.