Review of real-world evidence of dual inhibition of VEGF-A and ANG-2 with faricimab in NAMD and DME

Abstract

Management of vitreoretinal disorders (e.g., neovascular age-related macular degeneration [nAMD] and diabetic macular edema [DME]) have assumed the standard therapy of lifelong anti-VEGF injections with drugs like aflibercept, brolucizumab, ranibizumab and bevacizumab. However, the burden imposed on patients is a major deterrent for continual therapy and recovery. Faricimab, a bispecific antibody, blocking both VEGF-A and Ang-2 molecules, produces a comparable functional and anatomical results, with less injections, significantly reducing patient burden. Visual acuity, safety, adverse effects, and anatomical outcomes are discussed in the pivotal clinical trials (YOSEMITE/RHINE and TENAYA/LUCERNE), and early data from real-world studies (TRUCKEE, TAHOE, FARWIDE-DME, FARETINA and others). In YOSEMITE and RHINE, faricimab demonstrated non-inferior vision gains, better anatomical outcomes compared to aflibercept every 8 weeks. Faricimab in the personalized treatment interval (PTI), after week 96, achieved 12-week interval in 78.1% of the patients and 16-week interval in 62.3%. TENAYA and LUCERNE reported comparable best corrected visual acuity (BCVA) improvement and better anatomic outcomes during head-to-head phase, parallel to aflibercept, at its 8-week treatment schedule. Faricimab in the PTI regimen, after week 96 achieved 12-week interval in 77.8% of the patients and 16-week interval in 63.1%. Safety of faricimab has been comparable to aflibercept in these pivotal trials. Real-world data supports the data from the pivotal studies regarding the efficacy and safety profile of faricimab in heterogenous real world patient population. Moreover, in previously treated patients, it also demonstrated a faster fluid resolution, good safety profile. Considering faricimab has demonstrated anatomic and durability benefit in the treatment of nAMD and DME, additional data from ongoing extension clinical trials, AVONELLE-X and RHONE-X will help understand longer term outcomes for patients treated with faricimab as well as patients switching from aflibercept to faricimab after finishing the pivotal trials. Longer term data from the real-world studies will also continue to contribute to our understanding of long-term efficacy, safety and durability in the real world patient population.

Efficacy and safety of faricimab for neovascular age-related macular degeneration: a systematic review and network meta-analysis

“…The FARWIDE-AMD and the FARETINA-AMD studies found that visual acuity remained stable after three injections in previously treated patients with anti-VEGF and showed improvement in naïve patients. 84 85 This is also consistent with the reported improvement after three injections of clinical outcomes in the TRUKEE study, where the improvements were mainly in the previously untreated patients, with gains of 8.1 letters in BCVA and reductions in the retinal thickness of −80.1 µm. 86 Currently, real-world studies support our results on maintaining functional visual acuity outcomes and improving anatomical outcomes with the use of faricimab.…”

Advancements in the Treatment of Diabetic Macular Edema: Current Strategies and Future Directions

“…The safety profile of faricimab has been demonstrated to be favourable, with rates of inflammation and endophthalmitis comparable to those observed in other widely used treatments 25 .…”