Newly released 3-year data from the TRUCKEE study and additional analyses from the pivotal TENAYA and LUCERNE trials demonstrate faricimab's sustained efficacy and superior fluid reduction in patients with neovascular age-related macular degeneration (nAMD).
The TRUCKEE study, a real-world investigation presented at the Association for Research in Vision and Ophthalmology (ARVO) meeting, provides the longest follow-up data to date for faricimab in wet AMD patients. The retrospective chart review analyzed outcomes after nine injections across three patient groups: all-switch (n=436), aflibercept-switch (n=269), and treatment-naïve (n=61).
"We are now at 3 years, and we're seeing maintenance in vision and fluid status," said Hannah Khan, MPH, who presented the findings. "Right now we're looking at nine injections of faricimab with pretty significant maintenance of fluid and vision."
The study demonstrated that benefits from faricimab increased with continuous treatment, with a large proportion of patients achieving complete resolution of intraretinal fluid (IRF) or subretinal fluid (SRF). Importantly, the data showed potential for reducing treatment burden.
"We're also seeing an extension of treatment intervals," Khan noted. "As we move on through the study and we increase patients' injections, we are able to extend their intervals between injections."
Safety findings were reassuring, with low rates of idiopathic orbital inflammation and endophthalmitis. Only one case of nonocclusive vasculitis was reported across the study population.
Superior Anatomic Outcomes in Head-to-Head Comparison
A separate post-hoc analysis of the TENAYA and LUCERNE pivotal trials provides direct comparison data between faricimab and aflibercept during the initial 12-week dosing phase, when both treatments followed the same dosing schedule.
The analysis, led by Dr. Chui Ming Gemmy Cheung from the Singapore Eye Research Institute, found that faricimab demonstrated superior anatomic outcomes compared to aflibercept. At week 12, more patients achieved absence of SRF with faricimab (87.9% [95% CI, 85.4%-90.4%]) compared to aflibercept (79% [95% CI, 76%-82.1%]).
Similarly, the proportion of patients achieving absence of both IRF and SRF was higher with faricimab (77.2% [95% CI, 74%-80.4%]) versus aflibercept (66.5% [95% CI, 62.9%-70%]).
Faster Fluid Resolution and Greater Retinal Thickness Reduction
Among patients with IRF or SRF at baseline, the time to first absence of retinal fluid was shorter with faricimab. The 75th percentile of time to first absence of IRF and SRF was reached at week 8 with faricimab compared to week 12 with aflibercept.
Faricimab also demonstrated greater reductions in central subretinal thickness (CST) at all measured timepoints:
- Week 4: -128.8μm vs -115μm (difference: -13.8μm)
- Week 8: -140.3μm vs -127.7μm (difference: -12.6μm)
- Week 12: -145.4μm vs -133μm (difference: -12.5μm)
All differences were statistically significant (nominal P<0.0001).
Comparable Visual Acuity Gains
Despite the superior anatomic outcomes, both treatments showed comparable improvements in best-corrected visual acuity (BCVA). At week 12, the adjusted mean BCVA gain was 6.7 letters with faricimab and 5.9 letters with aflibercept.
"This more rapid improvement in anatomic outcomes with faricimab may result in early treatment interval extension, potentially leading to a reduction in treatment burden," Dr. Cheung and colleagues noted in their analysis.
Clinical Implications for Treatment Burden
The combined findings from these studies suggest faricimab may offer advantages in treating wet AMD, particularly in reducing treatment burden through extended dosing intervals.
TENAYA and LUCERNE previously demonstrated that faricimab could be administered at up to 16-week intervals without sacrificing efficacy compared to aflibercept given every 8 weeks. The new analyses provide mechanistic support for this finding, showing that faricimab's superior fluid resolution may enable longer treatment intervals.
For patients with wet AMD, who often require lifelong treatment with frequent injections, the potential for extended dosing represents a significant quality of life improvement while maintaining vision outcomes.
Mechanism of Action
Faricimab's dual mechanism of action may explain its superior fluid resolution. As the first bispecific antibody approved for ophthalmic use, faricimab simultaneously inhibits angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A), two key pathways involved in vascular permeability and neovascularization in AMD.
This dual inhibition appears to provide more comprehensive control of retinal fluid compared to anti-VEGF monotherapy with agents like aflibercept, potentially leading to more durable treatment effects and extended dosing intervals.
Future Directions
The 3-year TRUCKEE data and detailed anatomic analyses from TENAYA and LUCERNE provide valuable insights into faricimab's long-term efficacy and mechanism of action. As more patients complete extended follow-up in these and other studies, additional data will help refine optimal treatment protocols and patient selection criteria.
The potential for reduced treatment burden without compromising visual outcomes represents an important advancement in the management of wet AMD, a condition that affects approximately 1.1 million people in the United States alone.
