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24-month results from OAKS and DERBY show that pegcetacoplan significantly reduced GA lesion growth with both monthly and every-other-month dosing.
Positive, 24-month results from the phase 3 OAKS and DERBY trials suggest the benefit of pegcetacoplan injection (SYFOVRE) in slowing lesion growth in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).1
Published in The Lancet on October 20, every-other-month and monthly regimens of pegcetacoplan injection were each associated with a clinically meaningful reduction of GA lesion growth, with increasing effects over time, in a large population of ≥1,200 patients.2
“The increasing treatment effects of SYFOVRE over time with both monthly and every-other-month dosing are exciting to see and meaningful for the field,” said Charles Wykoff, MD, PhD, senior author and director of research, Retina Consultants of Texas, in a statement.1 “The vision loss caused by GA takes a tremendous toll on patients and their families, impacting independence and well-being. SYFOVRE is a major advance for patients living with the progressive and relentless disease.”
Pegcetacoplan injection initially received approval from the US Food and Drug Administration (FDA) in February 2023, marking the first approved therapy to treat GA secondary to AMD.3 A second complement inhibitor for GA treatment, avacincaptad pegol (IZERVAY) from Iveric Bio, was approved by the FDA in August 2023.4
Pegcetacoplan injection, designed to target C3, provides comprehensive control of the complement cascade and is the only treatment approved for use beyond 12 months for GA.3 FDA approval was granted based on results from the 24-month, multicenter, randomized, double-masked, sham-controlled, phase 3 OAKS and DERBY trials.
In OAKS and DERBY, patients aged ≥60 years with GA secondary to AMD were randomly assigned (2:2:1:1) to intravitreal 15 mg per 0.1 mL pegcetacoplan monthly or every other month, or monthly or every-other-month sham.2 The trials measured the change from baseline to month 12 in the total area of GA lesions in the study eye by fundus autofluorescence in the modified intention-to-treat population.
A total of 1258 patients with GA were enrolled in OAKS and DERBY between August 2018 - July 2020. In OAKS, the modified intention-to-treat population consisted of 614 (96%) of 637 patients: 202 received pegcetacoplan monthly, 205 received pegcetacoplan every other month, and 207 received sham. In DERBY, the modified intention-to-treat population comprised 597 (96%) of 621 patients: 201 received pegcetacoplan monthly, 201 received pegcetacoplan every other month, and 195 received sham.
Analysis of OAKS showed pegcetacoplan monthly and every other month significantly slowed GA lesion growth by 21% (absolute difference in least-squares: mean, –0.41 mm2; 95% CI, –0.64 to –0.18; P = .004) and 16% (–0.32 mm2: 95% CI, –0.54 to –0.09; P = .0055), respectively, compared with sham, at 12 months. In DERBY, pegcetacoplan monthly and every other month slowed GA lesion growth, although it did not reach significance, by 12% (–0.23 mm2; 95% CI, –0.47 to 0.01; P = .062) and 11% (–0.21 mm2; 95% CI, –0.44 to 0.03; P = .085), respectively, compared with sham.
At the 24-month mark, pegcetacoplan monthly and every other month slowed GA lesion growth by 22% (–0.90 mm2; 95% CI, –1.30 to –0.50; P <.0001) and 18% (–0.74 mm2; 95% CI, –1.13 to –0.36; P = .0002), respectively, in OAKS, compared with sham. In DERBY, pegcetacoplan monthly and every other month slowed GA lesion growth by 19% (–0.75 mm2; 95% CI, –1.15 to –0.34; P = .0004) and 16% (–0.63 mm2; 95% CI, –1.05 to –0.22; P = .0030), respectively, compared with sham.
Safety analyses at 24 months in OAKS reported serious ocular treatment-emergent adverse in 5 (2%) of 213 patients receiving monthly pegcetacoplan and 4 (2%) of 212 patients receiving every-other-month pegcetacoplan. In DERBY, 4 (2%) of 206 patients receiving monthly pegcetacoplan, and 2 (1%) of 208 patients receiving every-other-month pegcetacoplan experienced serious ocular treatment-emergent adverse events.
In addition, new-onset exudative AMD was reported in 24 (11%), 16 (8%), and 4 (2%) patients in OAKS receiving pegcetacoplan monthly, pegcetacoplan every other month, and sham, respectively, at 24 months. In DERBY, at 24 months, 27 (13%), 12 (6%), and 9 (4%) patients receiving pegcetacoplan monthly, pegcetacoplan every other month, and sham, respectively, reported new-onset exudative AMD. Across both trials, pegcetacoplan was considered to have an acceptable safety profile.
In an interview with HCPLive, Wykoff discussed the FDA approval of pegcetacoplan injection, highlighting the meaningful impact of the therapy for patients with GA, noting it the “most important advance in retina care in over a decade.”5 Based on findings from DERBY and OAKS, Wykoff expressed confidence in communicating to patients the efficacy of pegcetacoplan injection in slowing the progression of GA, with effects appearing to increase over time.
“It is really important that that gets communicated that the longer we treat these patients, we think that it will have a greater benefit on tissue preservation,” Wykoff said. “And over time, that will translate into improved visual function compared to where they would have been with natural history.”