The U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding Astellas Pharma's supplemental New Drug Application (sNDA) for avacincaptad pegol intravitreal solution (IZERVAY), intended for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The FDA's decision, announced on November 15, 2024, stems from statistical matters related to the proposed labeling language.
The sNDA sought to incorporate positive Phase 3 two-year data from the GATHER2 trial into the US prescribing information. The GATHER2 trial evaluated the efficacy and safety of monthly and every-other-month dosing regimens of avacincaptad pegol over a two-year period. The Prescription Drug User Fee Act (PDUFA) target action date for the decision was November 19, 2024.
According to the FDA, the sNDA could not be approved in its current form due to comments on a statistical matter related to labeling language proposed by Astellas. The agency clarified that its decision was not based on any concerns regarding the safety or benefit-risk profile of avacincaptad pegol in the treatment of GA secondary to AMD.
Avacincaptad Pegol's Clinical Profile
Marci English, senior vice president of biopharma and ophthalmology development at Astellas Pharma, stated that the company stands by the clinical profile of avacincaptad pegol. She emphasized that it is the only FDA-approved GA treatment that has consistently demonstrated a statistically significant slowing of GA progression across two pivotal Phase 3 studies.
Avacincaptad pegol was initially approved by the FDA in August 2023 for the treatment of GA secondary to AMD. GA, a manifestation of advanced AMD, is characterized by the loss of underlying blood vessels in the macula, leading to retinal tissue atrophy and irreversible vision loss.
GATHER1 and GATHER2 Trial Details
The efficacy of avacincaptad pegol was demonstrated in the GATHER1 and GATHER2 randomized, double-masked, multicenter Phase 3 trials. These trials compared monthly administration of 2 mg avacincaptad pegol with a sham procedure in patients with GA secondary to AMD. In both trials, patients were randomized to either avacincaptad pegol or sham monthly for the first 12 months, with 286 patients enrolled in GATHER1 and 448 in GATHER2.
Both pivotal studies met their primary efficacy endpoint, demonstrating a statistically significant reduction in GA area as measured by fundus autofluorescence (FAF) at baseline, 6 months, and 12 months. The safety profile was assessed in over 700 patients with GA across both trials. Common adverse reactions (≥ 5%) included conjunctival hemorrhage, intraocular pressure, and blurred vision.
Next Steps for Astellas
Astellas has announced its intention to seek further information from the FDA and to work closely with the agency to address the feedback provided. The company remains committed to the ophthalmology space and to advancing solutions for individuals suffering from GA.
English added, “While this is a disappointment for patients and physicians who rely on [avacincaptad pegol] for the management of a chronic, progressive disease that can lead to irreversible vision loss, Astellas is unwavering in our commitment to the ophthalmology space and will continue to work with the FDA to advance solutions for those suffering from GA.”
