FDA Approves Avacincaptad Pegol for Geographic Atrophy

The US Food and Drug Administration (FDA) has approved avacincaptad pegol (IZERVAY) for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).¹

The approval granted to Iveric Bio on Friday night marks the second indication for a drug to treat the progressive form of vision loss after the approval of fellow complement inhibitor pegcetacoplan injection (SYFOVRE) in February.² Different from pegcetacoplan, avacincaptad pegol targets the complement 5 (C5) pathway.

The indication additionally comes at a time of heightened scrutiny in the space of complement inhibitors for patients with GA; pegcetacoplan developers Apellis Pharmaceuticals announced last week their review of the product’s potentially associated risk of retinal vasculitis in treated patients, after the rare condition was reported in at least 7 patient eyes since April.³

Avacincaptad pegol’s approval by the FDA was supported by data from a pair of phase 3 clinical trials showing significant reduction in mean growth rate of GA area in patients at 12 months. In the pivotal GATHER2 trial, patients receiving the intravitreal injection therapy reported a mean 17.7% reduction in GA area growth over 12 months, with no observed events of endophthalmitis, intraocular inflammation, nor ischemic optic neuropathy^.4

GATHER trial program investigator Arshad M. Khanani, MD, MA, director of clinical research at Sierra Eye Associates, said in a statement accompanying the approval that the FDA’s approval of avacincaptad pegol is “great news for the retina community and our patients suffering from GA.”

"Geographic atrophy has a devastating impact on patients' lives and can lead to irreversible vision loss,” Khanani said. “As a C5 inhibitor, (avacincaptad pegol) has shown to slow GA progression by targeting the source of retinal cell death and may preserve the upstream benefits of the complement system.”

In an interview with HCPLive during the American Society of Retina Specialists (ASRS) 2022 Annual Meeting, David Lally, MD, an ophthalmologist with New England Retina Consultants, discussed new post-hoc analysis data from GATHER1 showing avacincaptad pegol was linked to reduced GA lesion growth across all distances from the foveal center point versus sham.⁵

The benefit appeared to be continued and sustained among patients treated with the C5 inhibitor.

“What we saw is that as the minimum distance from the foveal center increases at baseline, we saw that the effect from avacincaptad pegol treatment was greater and it was a linear relationship that we could see over time,” Lally said. “I think this is exciting new data and developments that not only do we know that natural history can be dependent on lesion focality, but also the effects of our treatment can be different depending on the baseline lesion focality.”

References

1. ^{Astellas Pharma. Iveric Bio Receives U.S. FDA Approval for IZERVAY™ (avacincaptad pegol intravitreal solution), a New Treatment for Geographic Atrophy. Press release. Published August 4, 2023. 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}
2. ^{Iapoce C. FDA Approves Pegcetacoplan Injection for Geographic Atrophy. HCPLive. Published February 17, 2023. https://www.hcplive.com/view/fda-approves-pegcetacoplan-injection-geographic-atrophy}
3. ^{Kunzmann K. Apellis Reviewing Retinal Vasculitis Cases in Pegcetacoplan-Treated GA Patients. HCPLive. Published July 31, 2023. https://www.hcplive.com/view/apellis-retinal-vasculitis-cases-pegcetacoplan-treated-ga-patients}
4. ^{Iapoce C. Topline Data from GATHER2 Report Positive Efficacy of Avacincaptad Pegol in GA Treatment. HCPLive. Published September 6, 2022. https://www.hcplive.com/view/topline-data-gather2-effect-avacincaptad-pegol-ga-treatment}
5. ^{Iapoce C. David Lally, MD: Avacincaptad Pegol Shows Reduction of GA Lesion Growth. HCPLive. Published July 16, 2022. https://www.hcplive.com/view/david-lally-md-avacincaptad-pegol-reduction-ga-lesion-growth}