David R. Lally, MD: What Led to the GATHER Trials for Avacincaptad Pegol


A review of the development of complement inhibitors and how the latest GATHER2 data support avacincaptad pegol for the treatment of geographic atrophy.

Geographic atrophy (GA) has long been an unchecked burden of disease progression among patients with age-related macular degeneration (AMD)—the most common cause of vision loss among older Americans.

But just as anti-VEGF agents and their supporting pivotal trials came to redefine capability in treating patient eyes with AMD a decade ago, complement inhibitors including avacincaptad pegol and their supporting research are looking to revolutionize the state of GA management.

In an interview with HCPLive, David R. Lally, MD, an ophthalmologist and investigator with New England Retina Consultants, described the historic burden of GA in impacted patients and the development of avacincaptad pegol—culminating in the pivotal findings from the GATHER trial program.

“It’s like losing film…in your camera,” Lally said while describing GA. “Patients develop severe loss of their central vision over time, and this is a huge unmet need, that as we know when geographic atrophy begins to develop, we currently have no FDA-approved treatments for impacting the disease.”

Lally added that clinicians previously learned from natural history studies that the lesions of geographic atrophy will typically enlarge over time and progressive central vision loss occurs over time. From genome-wide association studies, they also learned that common variants associated with GA development were found in the complement system, and from histopathology studies that there are abnormal levels of complement associated with the GA.

“(Avacincaptad pegol) binds and blocks C5, and prevents further propagation of the central pathway, or the common pathway of complement,” Lally said. “The hope is to reduce inflammation in the retina, reduce cell death, and try to preserve retinal tissue over time.”

In discussing the latest findings from the GATHER2 trial, presented at the American Academy of Ophthalmology (AAO) 2022 Annual Meeting this October, Lally highlighted the key efficacy and safety outcomes associated with avacincaptad pegol. In translating such findings to real-world use, he described the prospect of targeting GA with the agent as a “big change for treating physicians.”

“This is the first time ever that we have had 2 pivotal studies of which both show statistical significance in the effect of the therapy at reducing lesion size,” he said. “We’re excited and thrilled to have hopefully our first tool in the belt to impact this disease.”

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