Faricimab Improves Anatomical Outcomes, Extends Dosing in Meta-Analysis

A systematic review and meta-analysis revealed that faricimab showed significant benefit in improving central subfield thickness (CST) while reducing injection frequency, compared with other anti-vascular endothelial growth factor (VEGF) drugs, among eyes with retinal diseases.¹

The review of 7 randomized controlled trials (RCT) showed high-strength evidence showing that faricimab is non-inferior among patients with age-related macular degeneration (AMD) and diabetic macular edema (DME), regarding vision gains, including improvement in best-corrected visual acuity (BCVA).

“Faricimab improved anatomical outcomes and extended durability with dosing up to every 16 weeks, addressing a significant unmet need for durable therapies that optimize real-world outcomes, but more long-term follow-up studies are needed to support our conclusions,” wrote the investigative team, led by Aimin Ji, of the department of pharmacy at Seventh Affiliated Hospital of Southern Medical University.

Anti-VEGF therapies are widely utilized for the treatment of retinal diseases, but there are drawbacks, including the short half-life of anti-VEGF therapy and the notable treatment burden owing to frequent injections. To address these limitations, dual-action therapy approaches have been developed and approved by regulatory agencies. Faricimab, an intravitreal bispecific antibody inhibitor of angiopoietin-2 (Ang-2) and vascular endothelial growth factor A (VEGF-A), was first approved by the US Food and Drug Administration (FDA) in January 2022, for the treatment of DME and AMD.²

In this analysis, Ji and colleagues performed a systematic review and meta-analysis of RCT data to assess the efficacy and overall safety of faricimab among patients with neovascular AMD and DME.¹ Two independent reviews conducted a systematic literature search of PubMed, ScienceDirect, Cochrane Library, and ClinicalTrials.gov to identify RCTs published before January 2023.

Inclusion criteria included RCTs comparing faricimab with other anti-VEGF agents, patients with AMD or DME who required VEGF inhibition, or trials that included outcomes on BCVA and CST on optical coherence tomography, the incidence of serious ocular adverse events, and the proportion of patients gaining ≥15 ETDRS letters. The analysis used weighted mean differences and risk ratios to integrate the different RCTs.

After the screening was performed, reviews identified 4 RCTS with 1678 patients with AMD and 3 RCTS with 20 patients with DME for the meta-analysis. Among the population with AMD, high-strength evidence revealed a significant difference in the number of injections between faricimab and other anti-VEGF therapy (weighted mean difference, –2.42 [95% CI, –3.93 to –0.90]; P = .002).

On the other hand, the review showed consistent high-strength evidence that faricimab had similar effects on the mean change in BCVA (weighted mean difference, 0.01 [95% CI, –0.09 to 0.11]; P = .78) and on the mean change in CST (weighted mean difference, –0.09 [95% CI, –0.19 to 0.01]; P = .08). High-level findings showed no significant difference between faricimab and other anti-VEGF agents in gaining ≥15 letters (risk ratio [RR], 1.02 [95% CI, 0.84 to 1.26]; P = .81).

Over an average of 18 months, the review showed no significant differences in adverse events between faricimab and other anti-VEGF agents, including serious adverse events (RR, 0.91 [95% CI, 0.77 to 1.08]; P = .29), serious ocular adverse events (RR, 0.95 [95% CI, 0.62 - 1.44]; P = .80), and all-cause mortality (RR, 0.79 [95% CI, 0.47 - 1.31]; P = .36).

Among those with DME, across 3 trials, investigators observed a significant difference in CST (weighted mean difference, –22.41 [95% CI, –29.95 to –14.86]; P <.00001) and the injection frequency (weighted mean difference, –0.93 [95% CI, –1.3 to –0.54]; P <.00001). However, investigators identified no significant differences in BCVA change and gaining ≥15 letters, or in differences related to safety signals.

"These data provide evidence that vascular stabilization mediated through simultaneous inhibition of Ang-2 and VEGF-A restores retinal anatomic features and functions better than VEGF inhibition alone and highlights the potential of Ang-2 inhibition for patients with DME," investigators wrote.

References

1. _{Li G, Zhu N, Ji A. Comparative efficacy and safety of Faricimab and other anti-VEGF therapy for age-related macular degeneration and diabetic macular edema: A systematic review and meta-analysis of randomized clinical trials. Medicine (Baltimore). 2023;102(50):e36370. doi:10.1097/MD.0000000000036370}
2. _{Kunzmann K. FDA approves Faricimab for patients with wet AMD or DME. HCP Live. April 15, 2022. Accessed January 10, 2024. https://www.hcplive.com/view/fda-approves-faricimab-patients-wet-amd-or-dme.}