FDA Issues CRL to Avacincaptad Pegol sNDA for Geographic Atrophy

The US Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for the supplemental New Drug Application (sNDA) of avacincaptad pegol intravitreal solution (IZERVAY) for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).¹

Announced by Astellas Pharma on November 15, 2024, the sNDA was intended to include new positive Phase 3 2-year data in the US prescribing information. GATHER2 assessed the efficacy and safety of every month and every month dosing of avacincaptad pegol through 2 years.

Intended for a decision by its Prescription Drug User Fee Act (PDUFA) target action date of November 19, 2024, the FDA indicated it cannot approve the sNDA in its present form, owing to comments on a statistical matter related to labeling language proposed by Astellas. The agency outlined no comments on the safety or benefit-risk profile of avacincaptad pegol for GA secondary to AMD.

“Astellas stands by the clinical profile of [avacincaptad pegol], the only FDA-approved GA treatment that consistently demonstrated statistically significant slowing of GA across two pivotal Phase 3 studies,” Marci English, senior vice president of biopharma and ophthalmology development at Astellas Pharma, said in a statement.

Avacincaptad pegol was approved by the FDA in August 2023, and indicated for the treatment of GA secondary to AMD.² Progression of AMD, defined by the loss of underlying blood vessels in the macula, leads to thinning or atrophy of the retinal tissue. The presence of GA can further impact vision and lead to irreversible loss in these eyes.

In the GATHER1 and GATHER2 randomized, double-masked, multicenter Phase 3 trials, monthly administration of 2 mg avacincaptad pegol was compared with sham in patients with GA secondary to AMD. For the first 12 months, patients were randomized to either avacincaptad pegol or sham monthly, with 286 enrolled in GATHER1 and 448 enrolled in GATHER2.¹

Avacincaptad pegol met the primary efficacy endpoint in both pivotal study, based on a statistically significant reduction in GA area measured by fundus autofluorescence (FAF) at baseline, 6 months, and 12 months. Safety was assessed in more than 700 patients with GA across both trials, with the most common adverse reactions (≥ 5%) including conjunctival hemorrhage, intraocular pressure, and blurred vision.

In the release, Astellas has announced the company will seek further information from the FDA and their intention to work closely with the agency to address any relevant feedback.

“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,” English added.¹

References

1. _{Astellas provides update on IZERVAYTM (avacincaptad Pegol Intravitreal solution) supplemental new drug application. News | Astellas Pharma Inc. (2024, November 19). https://www.astellas.com/en/news/29576}
2. _{Kunzmann K. FDA approves Avacincaptad Pegol for geographic atrophy. HCP Live. August 5, 2023. Accessed November 22, 2024. https://www.hcplive.com/view/fda-approves-avacincaptad-pegol-geographic-atrophy.}