Two new studies found pegcetacoplan to be safe and effective at slowing GA growth rate through at least six months in a real-world setting and 36 months in an extended clinical trial.

Two new studies found pegcetacoplan to be safe and effective at slowing GA growth rate through at least six months in a real-world setting and 36 months in an extended clinical trial. Photo: Paul M. Karpecki, ODClick image to enlarge.

The first of two injectable drugs approved for geographic atrophy in 2023, pegcetacoplan (Syfovre, Apellis) has been used in clinical practice for over a year now, and curiosity about the new treatment’s long-term capabilities and real-world performance is growing among doctors. While clinical trials for the drug evaluated its effect through two years, a new extension study offers data out to three years. Additionally, a separate investigation documents the clinical outcomes of real-world patients treated with pegcetacoplan. Both studies, the results of which were presented on Sunday at ARVO 2024 in Seattle, delivered promising data on the treatment’s safety and efficacy.

The GALE three-year open-label extension study, as it’s called, involves 83% of the subjects (n=1,258) who participated in the pivotal phase III OAKS and DERBY trials for Syfovre, in which eyes were randomized 2:2:1:1 to pegcetacoplan monthly, pegcetacoplan every other month, sham monthly or sham every other month.1 In the GALE study, participants continue the same treatment regimen. The purpose of this research is to report on the efficacy and safety of long-term intravitreal pegcetacoplan treatment in GA patients.

The following results have been reported from the first 12 months of the GALE study:

  • Pegcetacoplan reduced GA lesion growth by 21% with monthly treatment and 17% with treatment every other month.
  • In eyes with nonsubfoveal GA, pegcetacoplan reduced lesion growth by 26% with monthly treatment and 22% with treatment every other month.
  • In eyes with subfoveal GA, pegcetacoplan reduced growth by 19% with monthly treatment and 16% with treatment every other month.
  • Severe visual impairment occurred in 6.4% of patients with monthly treatment, 9.6% with treatment every other month and 12.0% with sham treatment.
  • Between months 24 and 36, pegcetacoplan reduced GA growth by 35% with monthly treatment and 24% with treatment every other month.

So far in the extension study, the safety profile of pegcetacoplan is consistent with the initial studies. The researchers who presented this data at ARVO concluded that the current results support the intervention's long-term efficacy and safety in GA.

The second study on pegcetacoplan therapy for GA, presented by a different research group at ARVO, pulled its data from real-world patients. A total of 109 eyes from 83 patients with GA secondary to AMD were treated with 15mg of intravitreal pegcetacoplan and underwent SS-OCT angiography imaging before and during treatment to assess lesion size, the presence of nonexudative macular neovascularization (MNV) and the onset of exudation.2 In total, 510 intravitreal injections of pegcetacoplan were administered. In all patients, the growth rate of GA was evaluated for at least six months.

The following observations were collected in this real-world study:

  • One eye developed vitritis, which resolved with topical steroid therapy.
  • At baseline, 14 eyes had previously received anti-VEGF therapy, and nonexudative MNV was detected in one of these. In total, eight eyes had treatment-naïve nonexudative MNV at baseline.
  • Twelve percent of eyes developed exudation during follow-up, and 4% required anti-VEGF therapy.
  • The square root GA growth rate was 0.26±0.16mm/year for eyes with at least six months of follow-up.
  • The mean square root GA growth rate decreased by 34% after pegcetacoplan therapy.

Based on these findings, the research group concluded that pegcetacoplan therapy appears effective for slowing the growth of GA in a real-world setting, with outcomes similar to those reported in clinical trials. However, they note that longer follow-up is still needed.

Original abstract content ©2024 Association for Research in Vision and Ophthalmology.

1. Abbey AM, Wykoff CC, Heier JS, et al. Long-term efficacy and safety of pegcetacoplan over 36 months including 12-month results of the GALE open-label extension study. ARVO 2024 annual meeting.

2. Shen M, Hiya F, Berni A, et al. Real world experience with intravitreal pegcetacoplan for treating geographic atrophy in AMD. ARVO 2024 annual meeting.