Efficacy of Intravitreal Pegcetacoplan vs Avacincaptad Pegol in Patients With Geographic Atrophy

Purpose: To evaluate the efficacy of intravitreal (IVT) pegcetacoplan monthly vs avacincaptad pegol monthly (primary analysis), and pegcetacoplan every other month vs avacincaptad pegol monthly (secondary analysis), for geographic atrophy (GA). Methods: Matching-adjusted indirect comparisons (MAIC) were conducted across global phase 3 trials using individual patient data from 2 pegcetacoplan trials (OAKS, NCT03525613; DERBY, NCT03525600) and published aggregate data from the avacincaptad pegol GATHER2 trial (NCT04435366). GATHER2 inclusion and exclusion criteria were applied to the OAKS and DERBY individual patient data. Key baseline variables were balanced using propensity score weighting. GA lesion growth at month 12 was assessed. Results from the MAIC were combined using meta-analysis. Results: The primary analysis included 103 patients from OAKS and 102 patients from DERBY who met the GATHER2 inclusion and exclusion criteria, and 447 patients from GATHER2. In OAKS vs GATHER2, the adjusted difference in GA lesion growth at month 12 between pegcetacoplan monthly and avacincaptad pegol was -0.716 mm² (95% CI, -1.385 to -0.046; P = .04), statistically favoring pegcetacoplan monthly. In DERBY vs GATHER2, the adjusted difference was -0.234 mm² (95% CI, -1.354 to 0.885; P = .68), directionally favoring pegcetacoplan monthly. After meta-analysis, the pooled effect for pegcetacoplan monthly vs avacincaptad pegol was -0.589 mm² (95% CI, -1.164 to -0.014; P = 0.04), statistically favoring pegcetacoplan monthly. A numerically greater reduction in GA lesion growth was observed with pegcetacoplan every other month vs avacincaptad pegol monthly (95% CI, -1.130 to -0.300; P = .25). Conclusions: Matching-adjusted indirect comparisons support a greater reduction in GA growth with pegcetacoplan monthly vs avacincaptad pegol monthly and no significant difference between pegcetacoplan every other month and avacincaptad pegol monthly.