Astellas has received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) regarding its proposed label update for Izervay (avacincaptad pegol), a treatment for geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The update sought to incorporate data from the Phase 3 GATHER2 trial, potentially enhancing Izervay's competitive standing against Apellis' Syfovre (pegcetacoplan). The FDA indicated that it could not approve the application in its current form due to a "statistical matter related to labelling language proposed by Astellas."
Setback for Astellas
This decision marks another significant setback for Astellas, particularly after the recent withdrawal of Izervay's marketing application in the European Union. Izervay, a complement C5 inhibitor, has been available in the US since 2023 as a monthly injection for up to 12 months for GA secondary to AMD. The GATHER2 trial suggested potential benefits with less frequent dosing (every other month) and sustained efficacy over two years.
Competitive Landscape
Syfovre, a complement C3 inhibitor, is already approved with a flexible dosing frequency (every 25 to 60 days), supported by clinical data demonstrating benefits over two years. This dosing flexibility gives Syfovre a competitive advantage that Astellas aimed to address with the GATHER2 data.
The program was central to Astellas' $5.9 billion acquisition of Iveric Bio last year. Marci English, head of biopharma and ophthalmology development at Astellas, stated that the company stands by Izervay's clinical profile, highlighting its statistically significant slowing of GA across two pivotal Phase 3 studies. She added, "While this is a disappointment for patients and physicians who rely on Izervay... Astellas is unwavering in our commitment to the ophthalmology space and will continue to work with the FDA."
Market Impact
Both Izervay and Syfovre target a substantial market, with analysts previously forecasting blockbuster sales for both drugs. In the first six months of its fiscal year ending March 31, 2025, Astellas reported JPY 28.1 billion ($182 million) in Izervay sales. Apellis reported $152 million in U.S. sales of Syfovre in the third quarter of calendar 2024. However, Syfovre has faced some challenges related to reported side effects, leading to adjustments in sales forecasts.
