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Allen Hu, Daniel Esmaili, Ramiro Ribiero, Caleb Bliss, Daniel Jones, David M Brown; Safety of intravitreal pegcetacoplan in patients with neovascular age-related macular degeneration receiving anti-VEGF therapy. Invest. Ophthalmol. Vis. Sci. 2021;62(8):427.
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Pegcetacoplan (APL-2) is a C3 therapy targeting complement overactivation driving geographic atrophy (GA) progression. Neovascular age-related macular degeneration (nAMD) can coexist with GA. APL-203 was designed as an 18-month, Phase 1b/2, multicenter, open-label study evaluating the safety of monthly intravitreal (IVT) APL-2 for 12 months in patients with nAMD receiving anti-VEGF, with an additional 6 months of follow up.
Patients age ≥60 years with nAMD and BCVA of ≥24 ETDRS letters (20/320 Snellen equivalent) in the study eye were enrolled. Eyes had received ≥6 months of IVT anti-VEGF therapy (at ≤8-week intervals for the most recent 2 injections). At screening, response to anti-VEGF was confirmed by reduction in macular fluid or thickness on optical coherence tomography (OCT). The primary endpoint was the incidence and severity of ocular and systemic treatment-emergent adverse events (TEAEs). APL-2 was administered ≥30 minutes apart from anti-VEGF.
17 patients (mean 77.2 years; 58.8% men; 94.1% white) received ≥1 dose of APL-2. Mean baseline VA in study eyes was 69.5 EDTRS letters. The majority of TEAEs were either mild or moderate. Common ocular TEAEs included increased intraocular pressure (IOP), uveitis, and conjunctival hemorrhage. Mean IOP was generally unchanged, and no deaths occurred. Two TEAEs of mild ocular hypertension were controlled with IOP-lowering drugs. Decline in BCVA (≥15 letters) in the study eye was observed in 8 patients; 6 fully recovered. In the other 2 patients, BCVA loss at the last study visit was deemed related to an ocular AE (unrelated to APL-2) or nAMD progression. During the study, patients remained on monthly anti-VEGF therapy. All patients had received a lyophilized APL-2 formulation for up to 7 months with no events of intraocular inflammation (IOI). A liquid formulation was introduced mid-study in 4 patients who then developed events of mild to severe IOI. All these events were transient, without long-term sequelae, and likely caused by a low-level impurity in the active pharmaceutical ingredient of the liquid formulation. The study was subsequently terminated early because sufficient data were collected for the sponsor’s objectives.
Administration of APL-2 in combination with anti-VEGF therapy in patients with nAMD appears to be safe and well tolerated.
This is a 2021 ARVO Annual Meeting abstract.
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