What Avacincaptad Pegol Could Bring to Geographic Atrophy

Veeral S. Sheth, MD, MBA, discusses the potential value of complement inhibitors for the at-need patient population.

Complement inhibitor molecules are gaining significant steam in the prospective treatment of geographic atrophy (GA). In fact, some agents with evidenced mid-phase clinical data are progressing toward late-stage outcomes that have caught the interest of ophthalmologist in need for greater GA options.

One such agent is avacincaptad pegol (Zumira), a novel C5 inhibitor in development and investigation from Iveric Bio for the potential treatment of dry age-related macular degeneration (AMD), as well as GA secondary to AMD—a pair of unmet treatment indications relative to neovascular, or “wet,” AMD.

Previous phase 2/3 data from the GATHER1 trial showed 2 different monthly dose regimens of avacincaptad pegol were associated with up to a 28% reduction in GA lesion growth over 12 months, with favorable safety profiles.

Further GATHER1 data at 18 months—reported by Veeral S. Sheth, MD, MBA, Director of Clinical Research at the University of Retina and Macula Associates, at the Association for Research in Vision and Ophthalmology (ARVO) 2021 Meeting last June—showed the intravitreal injection therapy provided up to 30% reduction in GA lesion growth over 18 months, again with good tolerability and safety.

In an interview with HCPLive this week prior to even newer anticipated data for avacincaptad pegol, Sheth discussed the significantly unmet needs in GA, and how what complement inhibitors may deliver to the space feels like repeated history.

“We have nothing for these patients—they suffer this vision loss,” Sheth explained. “This time point feels a lot like what it felt like 15 years ago when we were getting our first anti-VEGF therapies and saying to people for the first time, ‘Hey, we can actually alter the course of your disease in a meaningful way.’”

Sheth also discussed how new post-hoc analysis data for avacincaptad pegol at the Angiogenesis, Exudation, and Degeneration 2022 Meeting this weekend as well as future research will “elucidate a little bit more on where we stand at this moment.”

Additionally, Sheth discussed the key values and machination of complement inhibitors, the disease progression of GA, and what other outcomes he hopes to observe with the drug class beyond the standard GA outcome of lesion growth reduction.

“I think we’re going to be looking at functional measures: reading speed, low luminance vision, you’re going to be looking at things like microperimetry—those are all things we’re going to be looking at,” Sheth explained. “We need to validate them as clinical endpoints.”