Faricimab Provides Similar nAMD, DME Outcomes at Significantly Fewer Injections

Faricimab was associated with non-inferior or improved central subfoveal thickness (CST) relative to competitor anti-VEGF therapies with extended dosing intervals in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME), according to findings from a new assessment.

In data from a systematic review and meta-analysis conducted by a team of investigators from Southern Medical University in Guangdong, China, faricimab was linked to similar outcomes in change in best corrected visual acuity (BCVA), gaining of ≥15 letters on the ETDRS chart, as well as CST improvement compared to other anti-VEGF therapies among patients with either nAMD or DME. What’s more, the dynamic agent was associated with significantly fewer injections versus the other treatment options, despite providing consistent efficacy and safety outcomes.

A team of investigators led by Guoxian Li, of the Department of Pharmacy at Southern Medical, sought to conduct a systematic review and meta-analysis of randomized clinical trials evaluating the efficacy and safety of faricimab. Originally approved by the US Food and Drug Administration (FDA) for the treatment of either AMD or DME in January 2022, faricimab is a first-of-its-kind retina therapy—targeting the angiopoietin 2 (Ang-2) as well as VEGF-A pathway, offering the prospect of dynamic mechanism compared to standard anti-VEGF monotherapies.

“Many systematic reviews have found evidence of a significant advantage of anti-VEGF agents over other therapies in AMD and DME, but no meta-analysis has been published to evaluate the overall efficacy and safety in Randomized clinical trials of Faricimab,” Li and colleagues wrote.

The team conducted an online search and review of relevant randomized clinical trials published prior to January 2023 assessing faricimab for the treatment of AMD and/or DME. Eligible trials included comparison of faricimab with other anti-VEGF therapies, or an analysis of patients with AMD or DME who required anti-VEGF therapy. Trials additionally had ≥1 outcome regarding BCVA, CST, gaining ≥15 letters on the ETDRS chart, or incidence of serious ocular adverse events.

The final literature review and analysis included 7 randomized trials of faricimab in 3798 patients; among them, 4 regarded treatment-naïve patients with nAMD and 3 regarded previously treated or treatment-naïve patients with DME.

nAMD Outcomes

Li and colleagues observed consistent, high-strength evidence that faricimab provided a similar effect on mean change in BVCA versus other anti-VEGF therapies among patient with nAMD (MD, 0.01; 95% CI, -0.09 to 0.11; P = .78). The team additionally reported high-strength evidence of no significant difference in ETDRS 15-letter improvement with faricimab (relative risk [RR], 1.02; 95% CI, 0.84 – 1.26; P = .81), as well as no difference in mean change in CST (MD, -0.09; 95% CI, -0.19 to 0.01; P =. 08).

In comparing faricimab versus other anti-VEGF drugs among patients with nAMD over a mean 18 months, investigators observed no significant differences in each of general adverse events (RR, 1.07; 95% CI, 0.98 – 1.17; P = .13), serious adverse events (RR, 0.91; 95% CI, 0.77 – 1.08; P = .29), nor general ocular adverse events (RR, 0.98; 95% CI, 0.93 – 1.03). Moderate-strength evidence, however, did support that patients with nAMD receiving faricimab had sigfnificantly fewer injections than patients receiving other anti-VEGF therapies (MD, -2.42; 95% CI, -3.93 to -0.90; P = .002).

DME Outcomes

In the 3 analyzed clinical trials assessing faricimab versus anti-VEGF therapies in patients with DME, investigators observed high-strength evidence of similar change in BCVA (MD, 0.78; 95% CI, -0.26 to 1.83; P = .14), as well as 15-letter gain in ETDRS (RR, 0.97; 95% CI, 0.83 – 1.14; P = .71). There was, however, high-strength evidence of significant improvement in mean CST change among patients with DME receiving faricimab versus other anti-VEGF therapies (MD, -22.41; 95% CI, -29.95 to -14.86; P <.00001).

Similarly to patients with nAMD, patients with DME reported no significant differences in general adverse events, serious adverse events, nor ocular adverse events when receiving either faricimab or other anti-VEGF therapies over a mean 18 months. And again, high-strength evidence supported a significant reduction in number of treatment injections of faricimab in such patients (MD, -0.93; 95% CI, - 1.33 to 0.54; P <.00001).

Conclusions

Investigators noted a number of limitations in their systematic review and meta-analysis. First, they acknowledged the heterogeneity in the number of injections for the treatment of both nAMD and DME. “Sensitivity analyses suggested that BOULEVARD for DME and STAIRWAY for AMD significantly affected the overall estimate of results,” they noted. “In AMD, STAIRWAY was a relatively small sample size and was injected every or 16 weeks, other trials were a larger sample size and were injected every 4 up to 16 weeks. Similarly, in DME, the BOULEVARD study was a short treatment duration of 20 weeks and injected every 4 weeks, and the other 2 trials were a longer treatment duration of 56 weeks and injected every 8 weeks or personalized treatment interval.”

Additionally, the team stressed a need to determine the long-term durability benefits of faricimab’s unique mechanisms of action in patients with chronic, progressive retina diseases such as nAMD and DME. Additionally, the COVID-19 pandemic may have caused negative impact on each of the observed clinical trials.

All the same, Li and colleagues concluded their first-of-its-kind systematic review and meta-analysis resulted in data supporting the hypothesis that dual pathway inhibition of Ang-2 and VEGF-A “promotes vascular stability beyond VEGF inhibition alone.”

“The extended durability response from faricimab could provide sustained efficacy with fewer injections, which may preserve visual gains in a clinical practice setting,” they wrote. “On average, patients require 7–8 injections during the first months of anti-VEGF therapy. In contrast, faricimab has clear advantages with a minimum of 4 injections in months.”

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. HCPLive. Published online January 28, 2022. https://www.hcplive.com/view/fda-approves-faricimab-patients-wet-amd-or-dme}