Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials

SPS commentary:

Faricimab is a bispecific antibody that acts through dual inhibition of both angiopoietin-2 and vascular endothelial growth factor A. In the personalised treatment interval (PTI) arm, faricimab dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. Both faricimab groups met the primary endpoint of non-inferior BCVA gains (YOSEMITE 10·7 ETDRS letters in the faricimab 8-week group, 11.6 in the treat-and-extend faricimab group, and 10.9 in the aflibercept group; RHINE 11.8, 10.8 and 10.3, respectively).

A related comment notes the faricimab PTI group achieved dosing intervals of 12 weeks or more in approximately 70% of patients and 16 weeks in approximately 50%. Although total adverse events were comparable, serious ocular events were higher in the faricimab groups (YOSEMITE 1.9% and 2.9% in the faricimab groups vs 0.6% in the aflibercept group; RHINE 2.8% and 3.1% in the faricimab groups vs 1.9% in the aflibercept group).

The results of two non-inferiority studies of faricimab in neovascular age-related macular degeneration, again in comparison to aflibercept, have also been published. In all studies, there was a high rate of major protocol deviations, in part driven by the pandemic; other limitations include the absence of a comprehensive published protocol and the industry-funded nature of the trials. The authors of the comment say further research is needed; 2-year results from all four studies will provide longer-term safety and durability data. Although pivotal aflibercept studies evaluated a fixed dose, most specialists favour a variable regimen, and it is not known how faricimab would compare with variably dosed aflibercept.