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Presented at ASRS 2023, results from a posthoc analysis of YOSEMITE/RHINE suggest a potential anti-fibrotic effect of faricimab versus aflibercept in eyes with DME.
Treatment with faricimab every 8 weeks (Q8W) reduced the risk of epiretinal membrane (ERM) formation by 52% compared to aflibercept Q8W in eyes with diabetic macular edema (DME), according to a novel posthoc analysis of the phase 3 YOSEMITE/RHINE trials.
The findings, presented at the American Society of Retina Specialists (ASRS) 41st Annual Meeting, reported the negative impact of ERMs on both vision and retinal anatomy, as eyes with ERMs experienced worse visual acuity and fluid outcomes, as well as a lower rate of dose extension to Q16W to Q16W. .
“In summary, this is a study that suggested the potential anti-fibrotic effect of faricimab and really stressed the potential impact of ERMs affecting vision, anatomy, and treatment durability,” Jeff Willis, MD, PhD, global development leader of Vabysmo at Genentech, told HCPLive in an interview.
There are limited phase 3 data on the impact of epiretinal membrane on visual acuity, durability, and anatomy in eyes with DME. In YOSEMITE/RHINE, the presence of ERMs in the central subfield on optical coherence tomography (OCT) detected at reading center screenings was included in the exclusion criterion for both trials.
A novel post-hoc analysis was performed to compare the incidence of ERM formation in eyes with DME treated with faricimab versus aflibercept over a 2-year period. The investigators noted, to their knowledge, this is the first time ERM development has been investigated and presented from a phase 3 intervention trial setting.
ERMs were defined as the presence of a membrane on the (ILM) causing significant distortion of macular architecture in the central subfield (center 1mm). Masked, independent ERM grading was performed at the reading centers at baseline and weeks 16, 48, 52, 56, 92, 96, and 100. Nearly 97% of YOSEMITE/RHINE patients did not have an ERM at baseline. Otherwise, study groups were well-balanced across baseline characteristics.
Upon analysis, through week 100, faricimab Q8W was associated with a 52% reduction in the risk of ERM formation compared to aflibercept Q8W (odds ratio [OR], 0.48; 95% CI, 0.29 - 0.81; P = .0055). Correspondingly, faricimab was also associated with reduced ERM formation in a treat-and-extend regimen versus aflibercept Q8W (OR, 0.65; 95% CI, 0.41 - 1.05; P = .0783).
In addition, the investigative team conducted a treatment-agnostic posthoc analysis of YOSEMITE/RHINE pooled data to determine how ERM development influences vision, anatomy, and durability outcomes. They noted due to the limitations of post-baseline subgroup analyses, no causal relationship can be concluded from the results.
This analysis indicated eyes that developed ERMs during the study period tended to have worse BCVA, as well as worse CST, at 2 years, than those that did not develop ERMs. The posthoc analysis also showed individuals who developed ERMs tended to have a greater presence of intraretinal (75.9% vs. 48.6%) or subretinal fluid (10.6% vs. 3.4%) at the 2-year mark.
Regarding durability, only 25% (7 of 28 eyes) of eyes that developed an ERM in the treat-and-extend arm could be extended to a Q16W dosing of faricimab. In eyes without an ERM, 64% (332 of 516) of treat-and-extend patients could be extended to Q16W dosing.
“From a clinical perspective, I think that this data set suggests there’s a potential antifibrotic effect, though, we need to do more research here and continue to validate this finding,” Willis told HCPLive.
For more insight into this analysis, watch the full interview with Dr. Willis below:
Disclosures: Jeff Willis MD, PhD, is an employee of Genentech, Inc.