Reduction in Pigment Epithelial Detachment Thickness with Faricimab vs Aflibercept 2 mg During Head-to-Head Dosing in TENAYA/LUCERNE

<h3>Purpose</h3> To evaluate the effects of dual angiopoietin-2 (Ang-2)/vascular endothelial growth factor (VEGF)-A pathway inhibition with faricimab versus VEGF pathway inhibition with aflibercept 2 mg on pigment epithelial detachment (PED) in patients with neovascular age-related macular degeneration (nAMD). <h3>Design</h3> TENAYA/LUCERNE (NCT03823287/NCT03823300) post hoc analysis. <h3>Participants</h3> Patients with treatment-naïve nAMD. <h3>Methods</h3> Patients were randomized 1:1 to faricimab 6 mg up to every 16 weeks (Q16W) (n=665) after 4 initial Q4W doses or aflibercept 2 mg Q8W (n=664) after 3 Q4W doses. PED was defined as retinal pigment epithelium (RPE) elevation width ≥350 μm and graded as predominantly/purely serous (serous PED) or predominantly/only fibrovascular (fibrovascular PED). Large PED definition: thickness ≥125 μm. <h3>Main Outcome Measures</h3> PED thickness change from baseline during initial 12-week head-to-head dosing, proportion of patients with serous PED at the end of head-to-head dosing, time to first reduction of maximum PED thickness by 50%. <h3>Results</h3> Baseline PED characteristics were similar between arms. At week 12, the adjusted mean decrease from baseline in maximum PED thickness was greater with faricimab than aflibercept 2 mg in eyes with large (–119.1 [n=500] vs. –101.4 μm [n=496]; nominal <i>P</i>=0.0028), serous (–136.1 [n=128] vs. –108.2 μm [n=114]; nominal <i>P</i>=0.0147), and any type (–87.9 [n=644] vs. –74.5 μm [n=638]; nominal <i>P</i>=0.0067) PED at baseline. The proportion of eyes with serous PED at baseline remaining serous at week 12 was lower with faricimab than aflibercept 2 mg (4.7% vs. 13.4%; nominal <i>P</i>=0.0258). In eyes with large PED at baseline, the cumulative incidence of PEDs achieving time to first reduction of maximum PED thickness by 50% at week 12 was 35.3% with faricimab versus 25.7% with aflibercept 2 mg. The corresponding incidence in eyes with serous PED at baseline was 61.1% with faricimab versus 51.8% with aflibercept 2 mg. The incidence of RPE tears was low (faricimab, 2.9%; aflibercept 2 mg, 1.5%). <h3>Conclusions</h3> In TENAYA/LUCERNE, dual Ang-2/VEGF-A inhibition with faricimab elicited greater improvements in PED outcomes versus aflibercept 2 mg during head-to-head dosing. These findings are consistent with the greater drying of retinal fluid with faricimab during head-to-head dosing, which may allow for rapid treatment interval extension.