Starting pegcetacoplan two years earlier preserved about three times more retina in geographic atrophy

Design

Phase 3 open-label extension of two randomised trials, 48 months

Population

Eyes with geographic atrophy from OAKS and DERBY continuing into GALE

Primary outcome

Geographic atrophy growth rate and retinal tissue preserved

Effect

Up to 24% slower growth vs projected sham; non-subfoveal early 3.16 mm² vs delayed 1.11 mm² preserved

GALE was the open-label extension of the phase 3 OAKS and DERBY trials of pegcetacoplan, a complement C3 inhibitor, for geographic atrophy. Eyes treated throughout had 48 months of therapy; eyes originally given sham crossed over at 24 months and had 24 months of treatment.

Over 48 months, continuous treatment reduced the growth rate of atrophy by up to 24% against projected sham, equivalent to 1.88 mm² of retina preserved. In non-subfoveal atrophy, early treatment preserved up to 3.16 mm² with monthly dosing, against 1.11 mm² with delayed treatment. The risk of progression to absolute scotoma at central test points was reduced by 32–43%. Safety was consistent with the parent trials.

The findings support starting before the fovea is involved if the drug is to be used at all. The comparison with 'projected sham' after crossover is a modelled estimate, the extension was open-label, and the drug slows anatomical growth rather than improving vision. Pegcetacoplan is FDA-approved; availability and cost elsewhere, including India, limit its use.

• Image and measure geographic atrophy with fundus autofluorescence at diagnosis
• Discuss complement inhibition before foveal involvement if it is available and affordable
• Tell patients that treatment slows loss of retina but does not restore vision
• Monitor for conversion to neovascular AMD during treatment

Why it matters

In a progressive disease with no way to recover lost tissue, the timing of treatment matters as much as the drug.

Don't overread it

Open-label extension with modelled comparisons — it slows atrophy growth but was not shown here to preserve reading vision.

The statistics, in plain English

'Projected sham' is a statistical extrapolation, because after 24 months there was no untreated group. The early-versus-delayed comparison is between originally randomised groups but after an open-label crossover, so it is weaker than the original trial comparison.

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