GALE: Pegcetacoplan Achieves Increasing Efficacy in Subfoveal Geographic Atrophy

Pegcetacoplan injection (SYFOVRE) achieved increasing efficacy and a visual function benefit in subfoveal geographic atrophy (GA) secondary to age-related macular degeneration (AMD), according to late-breaking data presented at the 128th Annual American Academy of Ophthalmology (AAO) Meeting.

“Pegcetacoplan is the only FDA-approved therapy to demonstrate efficacy in subfoveal GA, and we see increasing effects over time, through 36 months with as few as 6 injections per year,” said Dilsher Dhoot, MD, California Retina Consultants. “When it comes to visual function, we see a benefit demonstrated in subfoveal GA utilizing micropermitry with pegcetacoplan.”

The US Food and Drug Administration (FDA) approved pegcetacoplan injection for the treatment of geographic atrophy secondary to age-related macular degeneration (AMD) in February 2024. GA lesion location can affect growth rate, with non-subfoveal GA lesions growing more rapidly than subfoveal GA lesions. Participants in the pivotal OAKS and DERBY populations were heterogeneous, with approximately two-thirds of patients exhibiting subfoveal lesions.

At baseline in OAKS and DERBY (n = 765), approximately 82% (n = 624) of eyes with subfoveal GA had best-corrected visual acuity (BCVA) >35 ETDRS letters (20/200 legal blindness) and approximately 22% had vision >65 ETDRS letters (20/50). The mean baseline visual acuity was BCVA 52.3 ETDRS letters (20/100).

GALE is a large open-label extension of the pivotal trials and marked the longest clinical program in GA. Patients could enroll at the 24-month mark to continue pegcetacoplan treatment on the same regimen or cross over from sham to active treatment at the same treatment interval.

Efficacy analyses evaluated the change in the GA area based on the 12-month data from GALE, with 36 months of continuous pegcetacoplan treatment. Actual sham occurred from 0 to 24 months, while months 24 to 36 were a projected sham. Across the first year of GALE, the retention rate was approximately 92%.

Upon analysis at Month 36, the results in non-subfoveal GA (n = 286) revealed a 32% (P <.0001) reduction in GA growth in the pegcetacoplan monthly cohort and a 26% (P = .0002) reduction in the pegcetacoplan every other month cohort. In Year 3, pegcetacoplan achieved a 42% (P <.001) reduction in GA growth in the monthly cohort and a 28% (P = .0015) reduction in the every other month cohort.

In patients with subfoveal GA (n = 494), pegcetacoplan achieved increasing effects over time, with as few as 6 overall injections per year. At Months 0 to 36, reductions were 21% (P <.0001) and 19% (P = .0001) in the monthly and every month pegcetacoplan cohorts, respectively. At Year 3, the monthly cohort achieved a 31% (P <.0001) reduction in subfoveal lesions, while the every other month cohort showed a 25% (P <.0001) reduction.

Dhoot indicated that a comparison of study eyes to the subfoveal fellow eyes revealed results that were very similar to those of the projected sham comparator. Every-other-month treatment showed an 18% (P <.0001) reduction overall and monthly treatment showed a 26% reduction (P <.0001), remaining similar to the projected sham.

Overall, pegcetacoplan treatment preserved clinically meaningful retinal tissue in subfoveal GA, with increasing effect over time. At 36 months, 1.1 and 0.98 mm2 were preserved in the monthly and every other-month cohorts, respectively.

Regarding functional outcomes, a visual function benefit was observed in subfoveal GA with pegcetacoplan treatment, based on the number of new scotomatous points on microperimetry. There was a consistent signal at 12, 24 (P = .0238), and 36 (P = .0062) months, which was significant for the monthly cohort.

A post-hoc analysis of the central 4 macular loci revealed pegcetacoplan reduced the risk of progression to absolute scotoma in subfoveal GA over 2 years, with a 32% risk reduction in the monthly cohort and a 29% reduction in the every other month cohort. An analysis of 16 loci revealed similar risk reductions, with 43% in the monthly cohort and 54% in the every other month cohort.

Safety in the first 12 months of GALE remained consistent with the OAKS and DERBY trials, including safety events of interest, infectious endophthalmitis, ischemic optic nerve, and intraocular inflammation

“There were no safety events of occlusive or non-occlusive retinitis or vasculitis,” Dhoot added. “We have seen post-marketing safety of 1 out of 4000 per first injection rate of retinal vasculitis, which appears to be a first injection phenomenon.”

References

1. _{Dhoot D. 36-Month Efficacy and Safety of Continuous Pegcetacoplan Treatment for Subfoveal GA: GALE Open-Label Extension Study. Presented at the American Academy of Ophthalmology (AAO) 2024 Meeting. Chicago, Illinois. October 18-21, 2024.}