Four-Year Outcomes of Faricimab in Diabetic Macular Edema: Results from the RHONE-X Extension Trial

Summary

RHONE-X Vabysmo DME 4-year Long-term safety, efficacy, and durability via treat-extend Phase 3 open-label. YOSEMITE RHINE extension.

Abstract

Purpose: The RHONE-X study (ClinicalTrials.gov identifier, NCT04432831) evaluated long-term safety and tolerability (primary end points), and efficacy (exploratory end points) of faricimab, a dual angiopoietin-2 (Ang-2) and vascular endothelial growth factor A (VEGF-A) inhibitor, using a treat-and-extend (T&E) protocol in patients with diabetic macular edema (DME).

Design: Global phase 3, multicenter, nonrandomized, 2-year open-label extension study of the YOSEMITE and RHINE (ClinicalTrials.gov identifiers, NCT03622580 and NCT03622593, respectively) studies.

Participants: Of 1622 patients who completed YOSEMITE and RHINE, 1474 patients (91%) were included in the RHONE-X trial.

Methods: Patients transitioned from faricimab every 8 weeks (Q8W), faricimab T&E, or aflibercept 2.0 mg Q8W in YOSEMITE and RHINE to the RHONE-X study without requiring monthly initiation doses. All received faricimab T&E at up to 16-week intervals based on best-corrected visual acuity (BCVA) and central subfield thickness (CST), per YOSEMITE and RHINE criteria. Patients attended every month during the initial 4-month masked period, then only for T&E dosing visits (open-label arm). Analysis windows were defined for the RHONE-X study years 1, 1.5, and 2 to account for visit asynchronicity.

Main outcome measures: The primary end point was incidence and severity of ocular and nonocular adverse events (AEs). Exploratory end points included change from baseline BCVA and CST, proportion of patients with absence of DME (CST < 325 μm), and treatment durability.

Results: Overall, 1204 patients (82%) completed the RHONE-X trial. The incidence of AEs leading to treatment discontinuation (1.5%) and rates of intraocular inflammation (1.3%) were low. Overall, faricimab T&E maintained visual and anatomic improvements achieved in YOSEMITE and RHINE. Adjusted mean BCVA improvements from YOSEMITE and RHINE baseline to the end of the RHONE-X trial were +10.1 letters (faricimab T&E), +11.4 letters (faricimab T&E [prior Q8W]), and +9.5 letters (faricimab T&E [prior aflibercept]); CST reductions were -198.3 μm, -202.5 μm, and -204.9 μm, respectively. At study end, more than 90% of patients achieved DME absence, regardless of prior treatment. Median number of injections over the RHONE-X trial (2 years) were 7 (faricimab T&E), 8 (faricimab T&E [prior Q8W]), and 8 (faricimab T&E [prior aflibercept]). By the RHONE-X trial completion, approximately 80% of patients received faricimab at ≥Q12W intervals.

Conclusions: Faricimab, a dual Ang-2 and VEGF-A inhibitor, provided long-term safety, efficacy, and durability in patients with DME treated using a T&E regimen. Sustained visual and anatomic improvements were observed, with extended dosing intervals and reduced treatment burden. Faricimab was well tolerated, with a safety profile consistent with the YOSEMITE and RHINE trials.