medwireNews: The dual angiopoietin (Ang)-2 and vascular endothelial growth factor (VEGF)-A pathway inhibitor faricimab is noninferior to aflibercept for improving visual acuity in people with diabetic macular edema (DME), and an individualized dosing strategy could help reduce treatment burden, suggest findings from the YOSEMITE and RHINE trials.
“In light of these results and its novel mechanism of action, faricimab might herald an important shift towards multitargeted treatment strategies for patients with diabetic macular oedema,” write the study authors in The Lancet.
Charles Wykoff (Houston Methodist Hospital, Texas, USA) and team explain that anti-VEGF agents are the current standard of care for people with center-involving DME. However, they note that it is difficult to achieve optimal outcomes in clinical practice because these agents “often require close monitoring and injections every 4–8 weeks,” but real-world frequencies are “consistently lower than clinical trial protocols and labelled dosing schedules.”
The investigators therefore investigated the potential of faricimab, the first bispecific antibody designed for intraocular use, to reduce treatment burden and improve outcomes for people with DME.
For the two identically designed phase 3 studies, a total of 1891 adults with vision loss due to center-involving DME were randomly assigned to receive faricimab 6.0 mg every 8 weeks (after loading doses every 4 weeks from weeks 0–20), faricimab 6.0 mg per personalized treatment interval (PTI), or the VEGF inhibitor aflibercept 2.0 mg every 8 weeks (after loading doses every 4 weeks from weeks 0–16).
Wykoff et al note that the PTI strategy “was designed to test the durability of faricimab using methods similar to those common in clinical practice,” and dosing intervals were altered according to disease activity at clinic visits, with a minimum of 4 weeks and a maximum of 16 weeks. More than 70% of participants in the PTI group achieved dosing intervals of 12 weeks or longer at the 1-year follow-up, demonstrating “strong durability” of the agent, they say.
In YOSEMITE (n= 940), the adjusted mean improvement from baseline in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56, was 10.7 Early Treatment Diabetic Retinopathy Study (ETDRS) letters for patients given faricimab every 8 weeks and 11.6 ETDRS letters for those given PTI faricimab, compared with 10.9 ETDRS letters for those given aflibercept. The respective improvements in RHINE (n=951) were 11.8 and 10.8 versus 10.3 ETDRS letters.
These findings translated into average differences versus aflibercept of –0.2 ETDRS letters for faricimab every 8 weeks and 0.7 ETDRS letters for PTI faricimab in YOSEMITE, and corresponding differences of 1.5 and 0.5 ETDRS letters in RHINE, meeting noninferiority criteria for both faricimab regimens.
The researchers also found that reductions in central subfield thickness during 1 year of follow-up “consistently favoured faricimab over aflibercept,” and a higher proportion of faricimab-treated patients achieved absence of DME and absence of intraretinal fluid.
“[T]hese data support the hypothesis that dual pathway inhibition via Ang-2 and VEGF-A blockade promotes vascular stability beyond VEGF inhibition alone,” write the investigators.
They say that faricimab was well tolerated overall, “with an acceptable safety profile comparable with aflibercept.” Rates of adverse ocular events in the faricimab every 8 weeks, PTI faricimab, and aflibercept arms were 31%, 34%, and 33%, respectively in YOSEMITE and 43%, 37%, and 36% in RHINE.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group