Expanded Label for Avacincaptad Pegol Intravitreal Solution Receives FDA Approval

Updated February 13, 2025, at 11:25AM.

The FDA approved an expanded label application for avacincaptad pegol intravitreal solution (Izervay; Astellas Pharma Inc) for treatment of patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The approval does not limit duration of dosing, allowing providers and patients greater flexibility when managing GA.

AI depiction of an older woman's eyes | Image Credit: © nabila - stock.adobe.com

"We are pleased with the FDA's decision to extend the use of [avacincaptad pegol intravitreal solution] for longer-term administration—further solidifying [avacincaptad pegol intravitreal solution’s] status as a trusted choice for thousands of GA patients since its launch in 2023,” said Marci English, senior vice president, Biopharma and Ophthalmology Development, Astellas Pharma, in a press release. “To date, [avacincaptad pegol intravitreal solution] remains the only FDA-approved treatment to demonstrate a statistically significant slowing of GA across two pivotal studies."¹

AMD is a major cause of moderate to severe vision loss in aging adults, affecting over 1.5 million individuals in the US. However, about 75% of cases are believed to be undiagnosed, and without timely treatment, 66% of patients with GA will experience significant vision loss or blindness.^1,2

In AMD, the macula, which is responsible for central vision, loses retinal cells and underlying blood vessels, leading to atrophy of retinal tissues. GA is an advanced, progressive, and irreversible form of dry AMD characterized by atrophic lesions in the outer retina that affects almost 1 million individuals in the United States. Patients with GA have limited treatment options, and the primary goal of available agents is to slow progression of lesion growth as well as long-term preservation of retinal tissue.^1,3

In 2023, pegcetacoplan injection (Syfovre; Apellis Pharmaceuticals, Inc) became the first FDA-approved agent for patients with GA secondary to AMD. Later that year, avacincaptad pegol intravitreal solution received approval based on data from the phase 3 GATHER1 (NCT02686658) and GATHER2 (NCT04435366) clinical trials.^4-6

Avacincaptad pegol intravitreal solution is an eye injection and is a potent, selective inhibitor of C5, which plays critical roles in innate immunity and cell death. The GATHER clinical studies suggest that suppression of C5 helps slow the progression of retinal cell degeneration. Both trials met their primary end points, leading to the agent’s approval.²

The GATHER trials were randomized, double-masked, sham-controlled, multicenter phase 3 clinical trials evaluating the safety and efficacy of monthly 2 mg intravitreal administration of avacincaptad pegol in patients with GA secondary to AMD. The patients were randomized 1:1 to receive either 2 mg of avacincaptad pegol intravitreal solution or sham monthly (GATHER1, n = 286; GATHER2, n = 448). The primary efficacy end point for both trials was GA area measured by fundus autofluorescence at baseline, month 6, and month 12. Safety was evaluated in over 700 patients with GA across the 2 trials.²

Over a 12-month period, patients in both trials receiving avacincaptad pegol intravitreal solution achieved a statistically significant reduction of the rate of GA growth, with benefits seen as early as 6 months. In the first year of treatment, patients saw a 35% reduction in progression. The safety profile was also favorable, with at least 5% of patients reporting conjunctival hemorrhage (13%), intraocular pressure (9%), and blurred vision (8%) at 12 months.²

"This is a welcome update for retina specialists, providing continued management options for treatment of this chronic, progressive disease that can lead to irreversible vision loss," said Veeral S. Sheth, MD, MBA, FACS, FASRS, partner and director of Clinical Trials University Retina, in a press release.¹

The FDA's decision to expand the label for avacincaptad pegol intravitreal solution marks a significant advancement in the management of geographic atrophy secondary to AMD. By allowing for longer-term administration, this approval enhances treatment flexibility for both patients and providers, addressing a critical need in slowing disease progression.

REFERENCES

1. U.S. FDA approves expanded label for Astellas' IZERVAY™ (avacincaptad pegol intravitreal solution) for geographic atrophy. PR Newswire. February 12, 2025. https://www.prnewswire.com/news-releases/us-fda-approves-expanded-label-for-astellas-izervay-avacincaptad-pegol-intravitreal-solution-for-geographic-atrophy-302375403.html

2. Iveric Bio receives U.S. FDA approval for IZERVAY™ (avacincaptad pegol intravitreal solution), a new treatment for geographic atrophy. PR Newswire. August 4, 2024. Accessed February 13, 2025. https://www.prnewswire.com/news-releases/iveric-bio-receives-us-fda-approval-for-izervay-avacincaptad-pegol-intravitreal-solution-a-new-treatment-for-geographic-atrophy-301894042.html

3. Bakri SJ, Bektas M, Sharp D, et al. Geographic atrophy: Mechanism of disease, pathophysiology, and role of the complement system. J Manag Care Spec Pharm. May 2023. doi: 10.18553/jmcp.2023.29.5-a.s2

4. FDA Approves SYFOVRE™ (pegcetacoplan injection) as the first and only treatment for geographic atrophy (GA), a leading cause of blindness. Apellis. February 17, 2023. Accessed February 13, 2025. https://investors.apellis.com/news-releases/news-release-details/fda-approves-syfovretm-pegcetacoplan-injection-first-and-only

5. Zimura in participants with geographic atrophy secondary to dry age-related macular degeneration. Updated February 23, 2024. Accessed February 13, 2025. https://clinicaltrials.gov/study/NCT02686658

6. A phase 3 safety and efficacy study of intravitreal administration of Zimura (complement C5 Inhibitor). ClinicalTrials.gov identifier: NCT04435366. Updated December 12, 2024. Accessed February 13, 2025. https://clinicaltrials.gov/study/NCT04435366