Indications
Avacincaptad pegol is specifically indicated for the treatment of geographic atrophy (GA), a condition that occurs secondary to age-related macular degeneration (AMD). This medication aims to address the progressive nature of GA, an irreversible vision-loss condition, by targeting underlying pathological mechanisms.
Pharmacodynamics
The pathophysiology of age-related macular degeneration is closely linked to the complement system, particularly the cleavage of complement component C5 into C5a and C5b, culminating in the formation of the membrane attack complex (MAC). This process is a significant contributor to cellular damage in AMD. Research shows amass complement deposition in the retinas of AMD patients, and genetic analyses identified mutations in complement regulatory genes in approximately 50% of this population. Avacincaptad pegol works by inhibiting the cleavage of C5, thereby mitigating the inflammatory processes that lead to retinal cell injury and degeneration. Clinical studies, such as GATHER1 and GATHER2, have shown that treatment with avacincaptad pegol results in a reduced rate of geographic atrophy growth, with a 29% reduction for patients on a monthly regimen and a 20% reduction for those on a bi-monthly regimen.
Absorption
Following the administration of a single dose of avacincaptad pegol, the medication achieves peak plasma concentrations (Cmax) approximately seven days post-dose, with a mean concentration of 68.4 ng/mL in patients with neovascular AMD. The area under the curve (AUC) from zero to 28 days is calculated to be 1064 day·ng/mL for a 2 mg dose. Steady-state analyses predict a Cmax of 83.9 ng/mL with monthly administration. Importantly, systemic exposure to avacincaptad pegol is significantly lower than local vitreal concentrations, estimated to be about 7,000-fold less in plasma.
Metabolism
The metabolic pathway of avacincaptad pegol has not been fully elucidated. However, it is anticipated that the drug undergoes catabolism by endonucleases and exonucleases, resulting in shorter oligonucleotide fragments. This expected process is typical for compounds of this nature and suggests a predictable breakdown into biologically inactive forms.
Mechanism of Action
Avacincaptad pegol functions as an RNA aptamer and is characterized as a PEGylated oligonucleotide specifically designed to bind and inhibit the complement protein C5. By targeting and inhibiting C5, avacincaptad pegol effectively prevents its cleavage into C5a and C5b, which in turn diminishes the formation of the membrane attack complex (MAC).
