Geographic atrophy is an advanced form of dry age-related macular degeneration that
can lead to irreversible vision loss and high burden of disease. We aimed to assess
efficacy and safety of avacincaptad pegol 2 mg in reducing geographic atrophy lesion
growth.GATHER2 is a randomised, double-masked, sham-controlled, 24-month, phase 3
trial across 205 retina clinics, research hospitals, and academic institutions globally.
To be eligible, patients had to be aged 50 years or older with non-centrepoint-involving
geographic atrophy and best corrected visual acuity between 20/25 and 20/320 in the
study eye. Eligible patients were randomly assigned (1:1) to monthly avacincaptad
pegol 2 mg administered as a 100 μL intravitreal injection or sham for the first 12
months. Randomisation was performed using an interactive response technology system
with stratification by factors known to be of prognostic importance in age-related
macular degeneration. Patients, investigators, study centre staff, sponsor personnel,
and data analysts were masked to treatment allocation. The primary endpoint was geographic
atrophy lesion size measured by fundus autofluorescence at baseline, month 6, and
month 12. Efficacy and safety analyses were done in the modified intention-to-treat
and safety populations, respectively. This trial is registered with ClinicalTrials.gov,
NCT04435366.Between June 22, 2020, and July 23, 2021, 1422 patients were screened
for eligibility, of whom 448 were enrolled and randomly assigned to avacincaptad pegol
2 mg (n=225) or sham (n=223). One patient in the sham group did not receive study
treatment and was excluded from analyses. There were 154 (68%) female patients and
71 (32%) male patients in the avacincaptad pegol 2 mg group, and 156 (70%) female
patients and 66 (30%) male patients in the sham group. From baseline to month 12,
the mean rate of square-root-transformed geographic atrophy area growth was 0·336
mm/year (SE 0·032) with avacincaptad pegol 2 mg and 0·392 mm/year (0·033) with sham,
a difference in growth of 0·056 mm/year (95% CI 0·016-0·096; p=0·0064), representing
a 14% difference between the avacincaptad pegol 2 mg group and the sham group. Ocular
treatment-emergent adverse events in the study eye occurred in 110 (49%) patients
in the avacincaptad pegol 2 mg group and 83 (37%) in the sham group. There were no
endophthalmitis, intraocular inflammation, or ischaemic optic neuropathy events over
12 months. To month 12, macular neovascularisation in the study eye occurred in 15
(7%) patients in the avacincaptad pegol 2 mg group and nine (4%) in the sham group,
with exudative macular neovascularisation occurring in 11 (5%) in the avacincaptad
pegol 2 mg group and seven (3%) in the sham group.Monthly avacincaptad pegol 2 mg
was well tolerated and showed significantly slower geographic atrophy growth over
12 months than sham treatment, suggesting that avacincaptad pegol might slow disease
progression and potentially change the trajectory of disease for patients with geographic
atrophy.Iveric Bio, An Astellas Company.
