On August 4, 2023, the FDA approved avacincaptad pegol intravitreal solution (Izervay; Iveric Bio, an Astellas Company) for the treatment of patients with geographic atrophy secondary to age-related macular degeneration (AMD).
Avacincaptad pegol intravitreal solution is a complement C5 inhibitor and is the only drug approved for the treatment of geographic atrophy that has shown a significant (P<.01) reduction in the rate of disease progression at 12 months.
AMD is a major cause of moderate and severe loss of central vision in aging people. AMD-related geographic atrophy leads to irreversible loss of vision.
“Geographic atrophy [GA] has a devastating impact on patients’ lives and can lead to irreversible vision loss. As a C5 inhibitor, Izervay has shown to slow GA progression by targeting the source of retinal cell death and may preserve the upstream benefits of the complement system. The FDA approval of Izervay is great news for the retina community and our patients suffering from GA,” said Arshad M. Khanani, MD, MA, FASRS, Director of Clinical Research, Sierra Eye Associates, Reno, NV, in a press release.
The FDA approved avacincaptad pegol based on the safety and efficacy results of 2 pivotal, randomized, double-masked, sham-controlled, multicenter, phase 3 clinical trials—GATHER1 (NCT02686658), which enrolled 286 patients with geographic atrophy secondary to AMD and lasted 18 months, and GATHER2 (NCT04435366), which included 448 patients and lasted 12 months. Patients in both studies were aged 51 to 97 years (mean, 77 years). In both studies combined, a total of 292 patients (67 in GATHER1 and 225 in GATHER2) received treatment with avacincaptad pegol 2 mg and 332 patients (110 and 222, respectively) received a sham treatment.
For the first 12 months in both studies, patients were randomized to receive avacincaptad pegol 2 mg or a sham treatment monthly. The primary efficacy end points in both studies were based on the reduction in geographic atrophy area (as measured by fundus autofluorescence) with avacincaptad pegol versus the sham treatment at baseline, at 6 months, and at 12 months.
At 12 months, the rate of growth in the geographic atrophy area in GATHER1 was 1.22 mm2 with avacincaptad pegol versus 1.89 mm2 with the sham treatment (95% confidence interval [CI], 0.21-1.13); in GATHER2, the rates of growth were 1.75 mm2 versus 2.2 mm2 (95% CI, 0.12-0.63), respectively, which translated to a significant reduction with avacincaptad pegol in the rate of increase in geographic atrophy area of 0.10 mm annually (P<.01) in GATHER1 and of 0.05 mm annually (P<.01) in GATHER2. Overall, the slowing rate of geographic atrophy area with avacincaptad pegol was observed as early as within 6 months of receiving therapy, resulting in a 35% reduction in the first year of treatment in GATHER1 and a 18% reduction in GATHER2.
“Geographic atrophy can severely limit people’s ability to drive, read, and see the faces of their family and friends. This new treatment offers our patient community an important therapeutic option to potentially extend their ability to maintain independence,” noted Jason Menzo, Chief Executive Officer, Foundation Fighting Blindness, in a press release.
The most common (≥5%) adverse events at 12 months after receiving avacincaptad pegol in the 2 studies were conjunctival hemorrhage (13%), intraocular pressure (9%), blurred vision (8%), and choroidal neovascularization (7%). At any time during the GATHER2 study, patients who had choroidal neovascularization concomitantly received anti-VEGF therapy.
Avacincaptad pegol is contraindicated in patients with ocular or periocular infections and in patients with active intraocular inflammation.
The recommended dose of avacincaptad pegol is 2 mg (0.1 mL of 20-mg/mL solution), administered by intravitreal injection to each affected eye once monthly for up to 12 months.