Targeting Complement Factor D Reduces Progression of AMD-Related Geographic Atrophy
Science Translational Medicine
Published online June 21, 2017
Genetic studies of patients with age-related macular degeneration (AMD) have implicated dysregulation of the alternative complement pathway in the pathogenesis of geographic atrophy (GA). Yaspan et al. conducted a clinical trial of lampalizumab, an inhibitor of complement factor D, and noted a potential therapeutic effect on GA.
For this phase 2 study, the researchers compared lampalizumab to sham treatment in patients with GA secondary to AMD. Lampalizumab was administered by intravitreal injection monthly (n = 42) or every other month (n = 41); sham treatment was given at the same intervals (pooled control group, n = 40). The primary efficacy variable was the mean change in lesion area from baseline to 18 months, measured from fundus autofluorescence images.
Monthly treatment with lampalizumab demonstrated a reduction in lesion-area progression of 20% relative to sham treatment, indicating that the study’s prespecified significance level was achieved. Efficacy in the monthly lampalizumab arm was noted as early as month 6 and continued thereafter. Monthly lampalizumab treatment reduced progression of the GA area regardless of lesion size at baseline. In contrast, the area of GA enlarged in the pooled sham group.
In a subgroup of complement factor I (CFI) risk-allele carriers (representing 57% of all patients analyzed), monthly active treatment produced a 44% reduction in progression of the atrophic area; no treatment effect was apparent in risk-negative patients. Overall, lampalizumab demonstrated an acceptable safety profile throughout the 18-month study.
The original article can be found here.