Faricimab Rapidly Reduces Retinal Fluid in nAMD in TENAYA and LUCERNE

A recent post hoc analysis identified faricimab as exhibiting greater improvements in anatomic outcomes than aflibercept during the head-to-head testing phase of the TENAYA and LUCERNE trials in neovascular age-related macular degeneration (nAMD).

TENAYA and LUCERNE were randomized, double-masked, non-inferiority trials across 271 sites globally. Across both trials, a total of 1329 treatment-naïve patients with nAMD ≥50 years were randomized 1:1 to intravitreal faricimab 6 mg up to every 16 weeks, or aflibercept 2 mg every 8 weeks.2

In both trials, faricimab exhibited non-inferiority to aflibercept in best-corrected visual acuity (BCVA) change from baseline. Investigators determined that faricimab given at up to 16-week intervals demonstrated the potential to extend the time between treatments without sacrificing efficacy. However, neither trial directly compared the anatomic outcomes of either faricimab or aflibercept.2

“Direct comparisons in anatomic responses between faricimab and aflibercept across the full TENAYA/LUCERNE trial periods were limited because of differences in the agents’ dosing regimens per the study design,” wrote Chui Ming Gemmy Cheung, MBBS, Singapore Eye Research Institute, National University of Singapore, and colleagues. “However, during the first 8 weeks of the 12-week initial dosing phase of the trials, both arms received 3 once every 4 weeks (Q4W) doses, allowing for a head-to-head comparison.”1

TENAYA involved 334 patients in the faricimab cohort and 337 in the aflibercept cohort. LUCERNE involved 331 in faricimab and 327 in aflibercept.

At week 12 of the TENAYA and LUCERNE trials, more patients achieved an absence of SRF (87.9% [95% CI, 85.4%-90.4%] vs 79% [95% CI, 76%-82.1%]) and both IRF and SRF (77.2% [95% CI, 74%-80.4%] vs 66.5% [95% CI, 62.9%-70%]), with faricimab versus aflibercept, respectively. Among patients with IRF or SRF at baseline (n = 581 faricimab; n = 591 aflibercept), the 75th percentile of time to first absence of IRF and SRF was reached at week 8 with faricimab and week 12 with aflibercept. At week 12, the cumulative incidence of first-time absence of IRF and SRF was 85.5% (95% CI, 82.3%-88.1%) with faricimab and 75% (95% CI, 71.3%-78.3%) with aflibercept.1

Cheung and colleagues indicated comparable adjusted mean gains in BCVA from baseline with both faricimab and aflibercept at week 4 (+4.6 [95% CI, +4.0 to +5.2] and +4.0 [95% CI, +3.4 to +4.6] letters, respectively), week 8 (+5.8 [95% CI, +5.1 to +6.4] and +5.2 [95% CI, +4.5 to +5.8] letters, respectively), and week 12 (+6.7 [95% CI, +6.1 to +7.4] and +5.9 [95% CI, +5.2 to +6.5] letters, respectively).1

Further analysis showed greater adjusted mean reductions in CST (all nominal P <.0001) from baseline with faricimab than aflibercept at week 4 (-128.8 [95% CI, -133 to -124.6] vs -115 [95% CI, -119.2 to -110.8]; difference, -13.8 [95% CI, -19.7 to -7.8] µm), week 8 (-140.3 [95% CI, -144.2 to -136.4] vs -127.7 [95% CI, -131.6 to -123.8]; difference, -12.6 [95% CI, -18.2 to -7] µm), and week 12 (-145.4 [95% CI, -149.1 to -141.8] vs -133 [95% CI, -136.7 to -129.3]; difference, -12.5 [95% CI, -17.7 to -7.3] µm).1

Proportions of patients with an absence of IRF was comparable between faricimab and aflibercept arms; however, the proportion of patients with an absence of SRF was greater (all nominal P <.05) with faricimab than aflibercept (respective CMH-weighted estimates, 69.3% [95% CI, 65.9%-72.7%] vs 60.2% [95% CI, 56.6%-63.9%] at week 4, 82.2% [95% CI, 79.3%-85.1%] vs 75% [95% CI, 71.7%-78.3%] at week 8, and 87.9% [95% CI, 85.4%=90.4%] vs 79% [95% CI, 76%-82.1%] at week 12).1

According to the team, these data represent the inherent superiority of faricimab in treating nAMD, thanks to the reduced time to absence of retinal fluid, greater CST reductions, and greater mean gains in BCVA.

“When treated with faricimab, patients with IRF or SRF at baseline achieved first absence of retinal fluid faster than with aflibercept,” Cheung and colleagues wrote. “This more rapid improvement in anatomic outcomes with faricimab may result in early treatment interval extension, potentially leading to a reduction in treatment burden.”1

References

1. Cheung CMG, Lim JI, Priglinger S, et al. Anatomic Outcomes with Faricimab vs Aflibercept in Head-to-Head Dosing Phase of the TENAYA/LUCERNE Trials in Neovascular Age-related Macular Degeneration. Ophthalmology. 2025;132(5):519-526. doi:10.1016/j.ophtha.2024.11.023

2. Heier JS, Khanani AM, Quezada Ruiz C, et al. Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials. Lancet. 2022;399(10326):729-740. doi:10.1016/S0140-6736(22)00010-1