TENAYA and LUCERNE: Phase 3 Trials of Intravitreal Faricimab up to Every 16 Weeks for Neovascular Age-related Macular Degeneration
April 2022
Written by: Mohsin H. Ali, MD
Retina Group of Washington
Washington D.C.
Heier JS, Khanani AM, Quezada Ruiz C, Basu K, Ferrone PJ, Brittain C, Figueroa MS, Lin H, Holz FG, Patel V, Lai TYY, Silverman D, Regillo C, Swaminathan B, Viola F, Cheung CMG, Wong TY; TENAYA and LUCERNE Investigators. 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 Jan 21:S0140-6736(22)00010-1.
Background:
Faricimab is the newest FDA-approved intravitreal medication available for the treatment of both neovascular age-related macular degeneration and diabetic macular edema. Faricimab is a bispecific IgG monoclonal antibody that inhibits both VEGF-A as well as Angiopoetin-2 (Ang-2). Inhibition of Ang-2 helps reduce vascular leakage, neovascularization, and inflammation. This study summarizes the results of the TENAYA and LUCERNE phase 3 clinical trials investigating the 1-year efficacy and durability of faricimab in patients with neovascular AMD (nAMD) in comparison to aflibercept.
Design:
All patients had treatment-naïve choroidal neovascularization secondary to AMD with BCVA 78-24 ETDRS letters (20/32-20/320 Snellen equivalent). Patients were randomized to the following treatment regimens:
- Faricimab Group [n = 334 in TENAYA, n = 331 in LUCERNE]: Faricimab 6mg q4 weeks up to week 12 (4 injections), then
- At week 20, patients with active disease were given faricimab q8 weeks until week 60.
- At week 24, patients with active disease (excluding those already placed on the fixed q8 week regimen at week 20) were given faricimab q12 weeks up to week 60.
- At weeks 20 and 24, patients with inactive disease were continued on faricimab q16 weeks.
- Aflibercept Group [n = 337 in TENAYA, n = 327 in LUCERNE]: Aflibercept 2mg q4 weeks up to week 8 (3 injections) followed by q8 weeks until the study end.
Results:
Efficacy Data: The primary outcome was change in BCVA from baseline averaged over weeks 40, 44, and 48. The results showed that faricimab dosed up to every 16 weeks was non-inferior to aflibercept dosed every 8 weeks in achieving a mean change in BCVA in both TENAYA (5.8 letters versus 5.1 letters) and LUCERNE (6.6 letters versus 6.6 letters). Change in mean central subfoveal thickness (CST) was comparable between the faricimab groups (-136.8 μm in TENAYA and -137.1 μm in LUCERNE) and the aflibercept groups (-129.4 μm in TENAYA and -130.8 μm in LUCERNE).
Durability Data: By week 48, around 80% of patients treated with faricimab were on either q12-week or q16-week dosing. Specifically, q12-week dosing was achieved in 34% of patients in TENAYA and 32.9% of patients in LUCERNE; and q16-week dosing was achieved in 45.7% of patients in TENAYA and 44.9% of patients in LUCERNE.
Safety Data: Intraocular inflammation occurred with faricimab injections in 5 (1.5%) patients in TENAYA and 8 (2.4%) patients in LUCERNE. Intraocular inflammation occurred with aflibercept injections in 2 (0.6%) patients in TENAYA and 6 (1.8%) patients in LUCERNE. There was only 1 case of endophthalmitis and this occurred in the aflibercept group in LUCERNE.
Limitations:
The main limitation of this study is that aflibercept was dosed at fixed q8-week intervals (after the first 3 monthly injections) without allowing rescue treatments or extension, and this likely differs from the real-world clinical experience of retina specialists using aflibercept.
Summary:
The 1-year results of the TENAYA and LUCERNE trials show durable, non-inferior visual outcomes for faricimab dosed up to q16 weeks relative to aflibercept q8 weeks. It remains to be seen how the efficacy, durability, and safety of faricimab plays out in the real-world and during the personalized treatment interval (PTI) regimen that will be employed in year 2 of the trials.
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