Pegcetacoplan Treatment for Geographic Atrophy Due to Age-Related Macular Degeneration: A Plain Language Summary of the FILLY Study

Abstract

Summary What is this summary about? This is a summary of a publication about the FILLY study, which was published in Ophthalmology in 2020. The FILLY study looked at an investigational medicine called pegcetacoplan as a possible treatment for geographic atrophy. Geographic atrophy, also known as GA, is the late stage of an eye disease called dry age-related macular degeneration, also known as dry AMD. In people with GA, lesions form on a part of the back of the eye called the retina. GA lesions are patches of thin retina. Growth of GA lesions ultimately causes blindness, which cannot be reversed. There is currently no approved treatment for GA. Pegcetacoplan, also called APL-2, could be a possible treatment for GA. Pegcetacoplan is an investigational medicine, which means it has not yet been approved. It is currently being studied in clinical studies to see how well it works. What happened in the FILLY study? The FILLY study included participants with GA and tested how well pegcetacoplan worked compared to a sham injection (an injection that looks like the study treatment but does not have any medicine in it). The study also looked at how safe it was in adults with GA. What were the results? The main questions the researchers wanted to answer were: Did pegcetacoplan slow the growth of the study participants' GA lesions? ○ Yes. Overall, the researchers found that pegcetacoplan did slow the growth of the study participants' GA lesions. Did pegcetacoplan change the participants' vision? ○ No. Overall, the researchers found that pegcetacoplan did not change the participants' vision. What medical problems happened after the participants received pegcetacoplan? ○ The researchers kept track of any serious medical problems that happened during the study, also called serious adverse events. They also kept track of other medical problems that happened, or got worse, only at some point after the participants received the study treatment. These are called treatment emergent adverse events, also known as TEAEs. The serious adverse events and TEAEs that the participants had are described later in this summary. What do the results of the study mean? Overall, results from this study showed that participants who received pegcetacoplan had slower growth of GA lesions than participants who received the sham injection. After the participants had stopped receiving pegcetacaoplan, the effect of the treatment seemed to be reduced. Pegcetacoplan did not change how well the participants could see during their vision tests in this trial. ClinicalTrials.gov NCT number: NCT02503332

Single intravitreal administration of a tetravalent siRNA exhibits robust and efficient gene silencing in mouse and pig photoreceptors

“…Both cell types are believed to be important cells to be targeted to reduce retinal VEGF levels in these diseases. 38 Similarly, a new US Food and Drug Administration–approved drug that delays disease progression in the dry form of AMD targets the complement system in RPE cells, 39 , 40 with an injection frequency of every 4–8 weeks. The frequency of injections for these age-related illnesses is a burden to elderly patients.…”

Acetyl-CoA carboxylase Inhibition increases RPE cell fatty acid oxidation and limits apolipoprotein efflux

“…Complement factors accumulate in drusen and activation of the complement system contributes to AMD progression. The only FDA-approved treatments for geographic atrophy (which occurs in advanced dry AMD) are inhibitors of the complement proteins C5 and C3 (47, 48). Notably the complement system and lipoproteins interact.…”

Single intravitreal administration of a tetravalent siRNA exhibits robust and efficient gene silencing in rodent and swine photoreceptors

“…Both cell types are believed to be important target cell in reducing retinal VEGF levels in these diseases 36 . Similarly, a new FDA approved drug that delays disease progression in the dry form of AMD, targets the complement system in RPE cells 37,38 with an injection frequency of every 4-8 weeks. The frequency of injections for these age-related illnesses is a burden to elderly patients.…”