EURETINA 2021 Day 1: Apellis Phase 1b Safety Data & Phase 3 Topline Results

Kevin Ferenchak, MD
Vitreoretinal Surgery Fellow
Mayo Clinic

Dr. Eleonora Lad, MD, PhD, Associate Professor of Ophthalmology at Duke Eye Center, presented at Euretina 2021 and shared updated results of the phase 1b safety study of intravitreal pegcetacoplan (APL2, Apellis Pharmaceuticals) for geographic atrophy (GA), supporting the phase 3 DERBY and OAKS studies. To be considered for the trial, patients had to have a diagnosis of GA secondary to AMD, be 60 years or older, have no history of choroidal neovascularization, have ETDRS equivalent VA of approximately 20/320 or better, and have total GA of 1-7 disc areas. Pegcetacoplan is a complement (C3) inhibitor that is FDA approved for adults with paroxysmal nocturnal hemoglobinuria, and Apellis plans to submit a new drug application for the treatment of geographic atrophy to the FDA in the first half of 2022.

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The phase 3 DERBY and OAKS trials were double masked trials investigating the change in total area of GA lesions based on autofluorescence at one year after monthly or every other month intravitreal pegcetacoplan (15mg/0.1 mL) compared to sham. The phase 2 FILLY trial demonstrated safety with only one report of non-infectious intraocular inflammation out of about 1,500 injections, but the phase 3 trial was complicated early on by non-infectious inflammation due to an impurity associated with scale-up of manufacturing. The impurity was identified and removed, and the trial restarted successfully with no new cases of intraocular inflammation.

The Phase 1b analysis compared the rate of GA lesion growth in 10 study eyes treated with pegcetacoplan compared to untreated fellow eyes over two years, two study eyes converted to exudative AMD and GA grew significantly slower in study eyes. In a conversation about patient selection with Dr. Jeffrey Heier, MD of Ophthalmic Consultants of Boston, Dr. Lad said that there are studies underway to standardize the use of this medication in clinical practice, and patients who have lost central vision from AMD in the fellow eye or those who have high risk biomarkers for central progression would be ideal for treatments to reduce GA growth.

Phase 3 DERBY and OAKS Topline Results

Apellis released topline results for the Phase 3 DERBY and OAKS trials following, and completely separate from, Dr. Lad’s presentation. OAKS met primary endpoint compared to sham for both every-other-month and monthly injections with significant reduction in GA growth of 16% and 22%, respectively, compared to sham at one year. DERBY did not meet its primary endpoint of GA lesion growth.  Analysis of extrafoveal GA growth showed a 23% and 26% reduction in growth with every-other-month and monthly injections of pegcetacoplan, respectively. Eyes who had more frequent injections had an increased rate of new-onset exudation at rates of 2.4%, 4.1% and 6.0% with sham, every-other-month, and monthly, respectively, with no mention of statistical significance.