A matching-adjusted meta-analysis (NMA) presented at the 128th Annual Meeting of the American Academy of Ophthalmology (AAO) 2024 in Chicago, US, revealed that Vabysmo (faricimab) demonstrates superior reduction in central subfield thickness (CST) compared to Eylea HD (aflibercept 8mg) in patients with diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD). The analysis, presented by Dr. Jennifer I Lim, compared 12-week data from Phase III trials, offering insights into the comparative efficacy of these therapies.
Vabysmo, a dual inhibitor of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2), and Eylea HD, a higher dose formulation of the VEGF inhibitor aflibercept, are both approved for the treatment of DME and nAMD. While both therapies have been individually studied, direct comparative trials are lacking. This NMA aimed to address this gap by indirectly comparing the efficacy of the two treatments using data from relevant Phase III trials.
Meta-Analysis Methodology
The study compared data from the YOSEMITE/RHINE trials (Eylea vs. Vabysmo in DME) to the PHOTON trial (Eylea vs. Eylea HD in DME), and the TENAYA/LUCERNE trials (Eylea vs. Vabysmo in nAMD) to the PULSAR trial (Eylea vs. Eylea HD in nAMD). Eylea served as a common comparator, facilitating the comparison between Eylea HD and Vabysmo. The analysis focused on 12-week data to ensure consistent injection numbers across all treatment arms. Matching adjustments were applied to account for differences in baseline characteristics between trials, such as mean age, best-corrected visual acuity (BCVA), diabetic retinopathy severity scale (DRSS), and mean CST.
Key Findings
In DME patients, Vabysmo demonstrated a statistically significant greater reduction in CST compared to Eylea HD. Specifically, Vabysmo thinned the CST by 19μm more than both Eylea and Eylea HD from baseline to week 12. Similar results were observed in nAMD patients, with Vabysmo reducing CST by 19μm more than Eylea and 17μm more than Eylea HD. These findings suggest that Vabysmo exhibits superior drying effects compared to Eylea and Eylea HD in both indications.
Expert Commentary and Limitations
Key opinion leaders (KOLs) interviewed by GlobalData acknowledged the lack of head-to-head data between Eylea HD and Vabysmo, highlighting the challenges in comparing the therapies due to differing trial designs. While the NMA provides valuable insights, it is important to acknowledge its limitations. The analysis relied on aggregated data from the PHOTON and PULSAR trials, rather than individual patient data. Furthermore, the study may not have accounted for all influential differences in patient characteristics.
Implications for Retinal Disease Treatment
Despite these limitations, the meta-analysis supports the potential of Vabysmo's dual pathway inhibition in achieving greater anatomical improvements in DME and nAMD. Vabysmo's superior CST reduction further fuels the interest in its hallmark dual pathway inhibition. The results may influence treatment decisions for retinal specialists managing patients with these conditions.
