Four-year data from the phase 3 RHONE-X open-label extension (OLE) for faricimab-svoa (VABYSMO, Genentech, a member of the Roche Group) recently published in Ophthalmology demonstrated durable visual and anatomical benefits for patients with diabetic macular edema (DME).
First up: VABYSMO.
First approved by the FDA in 2022, VABYSMO is the first bispecific antibody (targeting dual angiopoietin-2 [Ang-2] and vascular endothelial growth factor A [VEGF-A] inhibitor) indicated for:
- Neovascular (wet) age-related macular degeneration (AMD)
- Diabetic macular edema (DME)
- Macular edema following retinal vein occlusion (RVO)
- Received approval in April 2026 for an extended label
Plus: A pre-filled syringe (PFS) version of the formulation was later approved in 2024.
And how is it administered?
Via intravitreal (IVT) injection, and the recommended dosage varies by indication (see its prescribing information [PI] for all three).
Now to the RHONE-X OLE study.
The multicenter, long-term OLE study (NCT04432831) enrolled 1,474 patients who completed the pivotal phase 3 YOSEMITE (NCT03622580) and RHINE (NCT03622593) trials, making it one of the largest long-term extension studies conducted in DME.
The setup: Masked period followed for first 16 weeks (after which the study design switched to open-label), in which participants received either:
- Faricimab (ie: VABYSMO), administered IVT
- Sham injection, administered IVT
Note: All participants were treated on a personalized treat-and-extend (T&E) regimen up to 16-week intervals based on best-corrected visual acuity (BCVA) and central subfield thickness (CST).
What were the main outcome measures?
Primary endpoints: Incidence and severity of ocular and nonocular adverse events (AEs)
The exploratory endpoints included:
- Change from baseline BCVA and CST
- Proportion of patients with absence of DME (CST < 325 μm)
- Treatment durability
And the findings?
Overall: 1,204 patients (82%) completed the 2-year extension, representing an overall 4-year treatment experience for many participants.
Visual acuity gains achieved during the original YOSEMITE and RHINE studies were largely maintained throughout the extension period.
Moreover: CST reductions exceeded 198 microns (μm) across all treatment groups at year 4, demonstrating sustained fluid control.
Let’s dig into the clinical data.
The adjusted mean BCVA improvements and CST reductions for each group were as follows:
- Faricimab T&E: +10.1 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters
- CST reduction: –198.3 μm
- Faricimab T&E (prior Q8W): +11.4 ETDRS letters
- CST reduction: –202.5 μm
- Faricimab T&E (prior aflibercept): +9.5 ETDRS letters
- CST reduction: –204.9 μm
In addition: More than 90% of patients achieved protocol-defined absence of DME by the end of the study, regardless of whether they had originally received faricimab or aflibercept.
Tell me more about durability.
In RHONE-X, patients required a median of 7 (faricimab T&E) to 8 (faricimab T&E [prior Q8W]) injections.
By the fourth year of treatment, approximately 80% of patients were being maintained on dosing intervals of at least 12 weeks, while more than 60% were receiving injections every 16 weeks.
Let’s close out with safety.
Adverse events (AEs) leading to treatment discontinuation occurred in 1.5% of patients, and long-term safety findings were broadly consistent with previous faricimab studies.
- There was an incidence of intraocular inflammation of 1.3% and no reported cases of retinal vasculitis or retinal occlusive vasculitis
- Investigators also reported low rates of treatment-related serious ocular AEs, and most inflammation-related events were mild or moderate and resolved during the study period
Any limitations?
A few … During the open-label T&E period, patients only attended visits when faricimab treatment was administered.
- What this means: Efficacy and safety data were not collected at monthly intervals, potentially limiting data points and necessitating analysis windows for comparisons of averages, rather than specific time points.
In addition: Because discontinuations in studies may correlate with poorer outcomes, the reported mean outcomes may only represent those who completed the study with better responses.
Take home.
The study authors concluded that the findings from the OLE RHONE-X trial demonstrated faricimab’s long-term efficacy, extended dosing intervals, and favorable safety profile support its role in the chronic management of DME.
See here for more coverage on VABYSMO—and prior long-term data findings.