Pegcetacoplan yields favourable outcome in patients with geographic atrophy

The complement C3 inhibitor pegcetacoplan appears to induce significant decreases in the growth of geographic atrophy (GA), according to data from a phase II study.

Two hundred forty-six patients with GA were randomized to receive intravitreal injections of 15-mg pegcetacoplan monthly (n=86) or every other month (EOM; n=79) or sham intravitreal injections monthly or EOM (pooled, n=81) for 12 months, with follow-up at months 15 and 18. Researchers used fundus autofluorescence imaging to measure area and growth of GA.

The primary efficacy endpoint of change from baseline to month 12 in the square root of the GA lesion area was met in both the active treatment arms. The GA growth rate decreased by 29 percent (95 percent confidence interval [CI], 9–49; p=0.008) and by 20 percent (95 percent CI, 0–40; p=0.067) in patients receiving pegcetacoplan monthly or EOM, respectively, relative to those who received sham treatment.

Posthoc analysis revealed that the beneficial effect with pegcetacoplan was greater in the second 6 months of treatment, with reductions of 45 percent (p=0.0004) in the monthly regimen and 33 percent (p=0.009) in the EOM regimen arms.

There were two cases of culture-positive endophthalmitis and a case of culture-negative endophthalmitis documented in the pegcetacoplan monthly arm. New-onset exudative age-related macular degeneration (AMD) occurred more frequently in pegcetacoplan-treated eyes (20.9 percent and 8.9 percent in monthly and EOM arms, respectively) than in sham-treated eyes (1.2 percent).

A late stage of AMD, GA is a major cause of blindness. Phase III studies should establish the safety and efficacy of local C3 inhibition with pegcetacoplan for treating GA, the researchers said.