Impact of Faricimab vs Aflibercept on Epiretinal Membrane Formation Over 2 Years in Eyes with DME in the YOSEMITE/RHINE Phase 3 Trials

Theme: Retina*
What: Retina
Part of: Retina II: Stamping out Blindness and Restoring Sight / Rétine II: Lutter contre la cécité et redonner la vue
When: 6/1/2024, 04:15 PM - 05:45 PM
Where: Room | Salle 713 AB

Abstract

Purpose 

We conducted a novel post-hoc analysis to compare incidence of ERM formation in eyes with diabetic macular edema (DME) treated with faricimab vs aflibercept over 2 years. We describe the impact of ERMs on BCVA, anatomy and treatment intervals.

 

Methods 

YOSEMITE/RHINE (NCT03622580/03622593) were randomized, double-masked, active comparator–controlled, phase 3 trials designed to assess efficacy, durability, and safety of faricimab in patients with DME. Patients were randomized 1:1:1 to faricimab 6.0 mg every 8 weeks (Q8W) after 6 initial Q4W doses, faricimab 6.0 mg treat-and-extend (T&E) after 4 initial Q4W doses, or aflibercept 2.0 mg Q8W after 5 initial Q4W doses. The protocol-driven T&E algorithm allowed dosing intervals to be extended to Q16W, maintained, or reduced to Q4W based on visual acuity and anatomic criteria. Presence of ERMs was an exclusion criterion for both trials. Masked, independent ERM grading (defined prior to study start as significant distortion of macular architecture in the central 1 mm of OCT images) was conducted at the Central Reading Centers (Duke and Vienna) at baseline and weeks 16, 48, 52, 56, 92, 96, and 100. The intent-to treat population included eyes with no baseline ERM.

 

Results 

Over 2 years, ERMs developed in 23/619 (3.7%), 31/618 (5.0%) and 45/604 (7.5%) of faricimab Q8W, T&E, and aflibercept Q8W eyes, respectively. Risk of ERM formation was lower for faricimab Q8W vs aflibercept (HR 0.48; 95% CI 0.29, 0.80; nominal P=0.0039). The corresponding data for T&E patients vs aflibercept were HR 0.65 (95% CI 0.41, 1.03; nominal P=0.0644). Using a treatment agnostic approach, at year 2, eyes that developed ERMs during the study tended to have worse BCVA and CST outcomes than those that did not develop ERMs. Similarly, eyes that developed ERMs also tended to have higher rates of intra- (63/83; 75.9% vs 649/1336; 48.6%) and sub-retinal fluid (9/85; 10.6% vs 47/1372; 3.4%) at 2 years than those without ERM. Among faricimab-treated eyes in the T&E arm, dosing was extended to Q16W in a larger proportion of eyes without ERMs (332/516; 64.3%) than those with ERMs (7/28; 25%).

 

Conclusions 

For the first time, we have demonstrated a potential anti-fibrotic effect of faricimab vs aflibercept in an analysis of pooled YOSEMITE/RHINE trial data from eyes with DME. ERMs were associated with numerically worse visual acuity, worse anatomic outcomes, and a lower rate of dose extension to Q16W. 

 

 

Presenter(s)

Presenting Author: Peter Kertes

Additional Author(s):

Yuichiro Ogura, Genentech

Gábor Deak, Vienna Reading Center, Medical University of Vienna, Austria

Kara Gibson, Roche Products Ltd., Welwyn Garden City, UK

Ursula Schmidt-Erfurth, Department of Ophthalmology, Medical University of Vienna, Austria.

Tracey Wang, Hoffman-La Roche Pharmaceuticals Canada

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