Study Population

• 448 patients randomly assigned in a 1:1 protocol: Avacincaptad pegol 2mg (n=225) and Sham injection (n=223).
• Inclusion criteria:
  • At least 50 years of age
  • Non-center involving geographic atrophy
  • BCVA 20/25 - 20/320 in the study (80-25 ETDRS letters)
  • GA within 1500 um from center of the fovea with total area of 2.5-17.5 mm² (determined by screening autofluorescence images)
  • For multifocal lesions, one or more lesions had to be at least 1.25 mm² (0.5 disc areas)
• Exclusion criteria:
  • Macular atrophy secondary to any condition other than ARMD in either eye
  • Receipt of any previous treatment of ARMD or any previous intravitreal treatment for any indication in either eye apart from oral vitamin or mineral supplements
  • Presence of neovascularization in either eye

Randomization Scheme/Study Interventions

• Randomized 1:1
• Intravitreal avacincaptad pegol monthly for 1 year
• Sham monthly for 1 year
• At month 12 randomization was repeated for patients receiving avacincaptad pegol to:
  • Continued monthly avacincaptad pegol
  • Every other month through month 23
• Stratification based on poor prognostic factors for ARMD:
  • Baseline VA of 50 ETDRS letters (20/100 Snellen VA equivalent) vs. 50 or more ETDRS letters
  • Size of geographic atrophy (< 4 disc areas vs. > 4 disc areas)
  • Pattern of fundus autofluorescence at junctional zone of GA (none vs. focal vs. banded or diffuse)

Endpoints

• Primary endpoint: Reduction in mean rate of GA growth (slope) at month 12 of avacincaptad pegol compared to sham was achieved (Avacincaptad pegol 0.336mm/year vs sham group 0.392 mm/year), which was ~14% difference between the two groups.
• Secondary Endpoints:
  • No difference in BCVA or low-luminance BCVA between either avacincaptad group and the sham group.
  • Loss of 15 or more ETDRS letter from baseline was effectively halved in the avacincaptad pegol group over 12 months (hazard ratio of 0.41).
  • Post hoc analysis: mean change in observed GA area from baseline to month 12 was 1.936 mm² for avacincaptad pegol 2 mg and 2.341 mm² for sham (17% difference).

Safety

• Ocular treatment-emergent adverse events were 49% (110 patients) in avacincaptad pegol 2mg vs 37% (n=83) in the sham group (>2% rates in study eye included conjunctival hemorrhage, hyperemia, punctate keratitis, increased IOP, macular neovascularization, dry eye, eye pain, vitreous detachment, and cataract).
• 21 (9%) patients in the avacincaptad pegol 2 mg group versus 2 (<1%) developed increased intraocular pressure. Most occurred after the injection and were transient.
• Macular neovascularization occurred in 15 patients (7%) in the avacincaptad pegol 2mg group and 9 patients (4%) in the sham group. Exudative macular NV occurred in 11 (5%) of avacincaptad pegol group and 7 (3%) in the sham group.
• There were no events of endophthalmitis, intraocular inflammation, or ischaemic optic neuropathy in either treatment group.

Conclusions

• Monthly avacincaptad pegol 2 mg demonstrated slower GA growth over 12 months (~14%) when measured in lesional area size compared to control cohort.