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Phase II study results on intravitreal (IVT) pegcetacoplan (a synthetic cyclic peptide) for the treatment of geographic atrophy (GA) secondary to ARMD

A Phase II study investigating intravitreal pegcetacoplan for the treatment of geographic atrophy (GA), secondary to age-related macular degeneration (AMD), has announced the reporting of statistically significant reductions in the growth of GA, compared with sham treatment.  Results, published in the journal Ophthalmology (article in press, 2019), showed the GA growth rate was reduced by 29% (95% confidence interval [CI], 9-49; P= 0.008) and 20% (95% CI, 0e40; P= 0.067), compared with a sham treatment group. In addition, post hoc analysis showed that the effect was greater in the second 6 months of treatment, with observed reductions of 45% (P=0.0004) and 33% (P=0.009) for pegcetacoplan monthly and EOM (every other month), respectively.


The Phase II study is a prospective, multi-center, randomized, single-masked, sham-controlled trial to assess the safety, tolerability and evidence of activity of multiple IVT injections of pegcetacoplan in subjects with GA associated with Age-Related Macular Degeneration. The clinical trial evaluated pegcetacoplan in 246 patients at over 40 clinical sites in the United States, Australia and New Zealand.  Patients were diagnosed with GA associated with age-related macular degeneration in the study eye and met all inclusion/exclusion criteria included in the study.  In the RCT, registered at, the experimental study is a synthetic cyclic peptide conjugated to a polyethylene glycol (PEG) polymer that binds specifically to complement C3 and C3b.  As known, the complement system plays critical roles in both innate and adaptive immunity, contributing to immune surveillance, inflammation, and homeostasis via 3 different activation pathways (classical, alternative, and lectin) and numerous effector molecules.  According to the researchers, the diverse functions of the peptide include recruitment and activation of immune cells, opsonization of pathogens to target them for phagocytosis, and direct destruction of pathogens by the membrane attack complex.


In conclusion, the pegcetacoplan clinical trial represents the first study demonstrating that C3 inhibition can slow the progression of GA reducing significant GA lesion growth during 12 months of therapy.  In particular, study during the latter 6 months of the term showed an acceptable safety profile may now proceed to Phase 3 studies.  Commenting on the study the researchers stated that “these studies will define the efficacy and safety profile of pegcetacoplan further as a treatment for patients with GA, a blinding disease with no approved therapies”.