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

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.

Five-year outcomes of intravitreal drug therapy for neovascular age-related macular degeneration in eyes with baseline vision 20/60 or better.

OBJECTIVE: To assess outcomes in treatment-naive eyes with neovascular age-related macular degeneration (nAMD) and good baseline visual acuity (VA) treated using a treat-and-extend (T&E) regimen with intravitreal aflibercept, ranibizumab, or bevacizumab. DESIGN: Single center, retrospective, observational case series. PARTICIPANTS: Ninety-one patients (93 eyes) with nAMD and baseline VA ≥20/60 followed for ≥1 year after the first intravitreal injection. Minimum of 6 (first year) and 3 (subsequent years) and maximum of 12 injections per 12 calendar months. INTERVENTION: Intravitreal aflibercept 2.0 mg, ranibizumab 0.5 mg, or bevacizumab 1.25 mg. Three monthly injections. Treatment interval extended in 2-week increments after resolution of macular edema and reduced in 2-week increments if edema recurred; maximum interval of 12 weeks. Medication changed if edema recurred during and persisted after three monthly injections of original agent. MAIN OUTCOME MEASURES: VA maintenance over time. Total number of injections received by year of treatment. RESULTS: Ninety-three eyes were analyzed. Pretreatment VA was 20/20-20/25 (N=16), 20/30-20/40 (N=47), and 20/50-20/60 (N=30). Mean follow-up was 3.2 years. Follow-up by year was 93, 73, 65, 44, and 26 eyes for years 1-5, respectively. Mean number of injections during years 1-5 was 7.9, 5.9, 5.6, 5.9, and 6.0, respectively; mode number of injections was 7, 5, 3, 6, and 4, respectively. For years 1-5, percent of all eyes at or above baseline was 70%, 66%, 65%, 59%, and 58%, respectively; percent ≥20/60 was 86%, 88%, 86%, 84%, and 77% for years 1-5. For eyes with baseline VA ≥20/40, percent of eyes at or above baseline was 83%, 82%, 81%, 68% and 76% for years 1-5, respectively. CONCLUSION: Using a T&E intravitreal injection protocol, more than 75% of treatment-naive eyes with nAMD and baseline VA ≥20/60 can maintain VA ≥20/60 over 5 years.

New Therapies of Neovascular AMD beyond Anti-VEGF Injections.

Neovascular age-related macular degeneration is a leading cause of vision loss among the aging population. The current standard of care to treat neovascular age-related macular degeneration is inhibiting vascular endothelial growth factor (VEGF) through intravitreal injections. Recent studies have demonstrated that the tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 2 (Tie2) pathway also plays a critical role in angiogenesis and vascular stability. Additionally, newly developed treatment delivery systems have been designed to greatly reduce the frequency of injections. In targeting the Tie2 pathway and utilizing a sustained release delivery system, patients may experience improved visual outcomes and a reduced burden of treatment.