Abstract
Purpose :
Avacincaptad pegol, a polyethylene glycol-conjugated oligonucleotide, is a potent C5 inhibitor delivered via a 100 µl intravitreal injection. The 18-month results of GATHER1, a randomized, double-masked, multi-national, sham-controlled clinical trial evaluating avacincaptad pegol for treatment of geographic atrophy (GA) secondary to age-related macular degeneration, are reported here.
Methods :
Patients were randomized to avacincaptad pegol 1 mg, avacincaptad pegol 2 mg, avacincaptad pegol 4 mg or sham injection. GA progression was evaluated as a change in GA lesion area over 18 months measured by fundus autofluorescence; square-root transformation was applied to mitigate the impact of baseline factors on GA growth. Other assessments included visual function (best-corrected visual acuity and low-luminance visual acuity) and safety analysis.
Results :
The least-squares mean change from baseline to month 18 in square-root GA lesion area was 0.599 mm in sham-treated patients vs 0.430 mm in avacincaptad pegol 2 mg-treated patients (28% reduction; p<0.0014). The least-squares mean change from baseline to month 18 in square-root GA lesion area was 0.559 mm in sham-treated patients vs 0.391 mm in avacincaptad pegol 4 mg-treated patients (30% reduction; p<0.0021). There were no significant differences in best-corrected visual acuity or low-luminance visual acuity between avacincaptad and sham-treated patients. Avacincaptad pegol was generally well tolerated after 18 months of administration, with no drug-related adverse events or trial discontinuations.
Conclusions :
Intravitreal avacincaptad pegol resulted in a decrease in the rate of GA lesion growth over 18 months of treatment versus sham injection. GATHER2, a second pivotal clinical trial comparing avacincaptad 2 mg vs sham, has been initiated and is currently enrolling patients.
This is a 2021 ARVO Annual Meeting abstract.