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John Wells, MD, presents efficacy, durability, and safety findings from phase 3 YOSEMITE and RHINE trials during the virtual ARVO meeting.
The 1-year results of the ongoing 2-year YOSEMITE and RHINE trials showed favorable results for faricimab for treating diabetic macular edema (DME). The visual gains achieved with every-16-week dosing were non-inferior to those of aflibercept (Eylea, Regeneron Pharmaceuticals) dosed every 8 weeks.
The anatomic gains also favored faricimab compared with aflibercept. Faricimab also demonstrated a good safety profile with very low rates of inflammation. John Wells, MD, from the Palmetto Retina Center, West Columbia, South Carolina, presented the results at the Association for Research in Vision and Ophthalmology’s (ARVO) virtual 2021 annual meeting on behalf of the YOSEMITE and RHINE investigators.
“Faricimab is the first bispecific antibody to target both anti-Angiopoietin-2 and anti-vascular endothelial growth factor (VEGF) that may reduce inflammation and vascular leakage, promote vascular stability, and improve outcomes beyond anti-VEGF monotherapy for DME,” he said.
The YOSEMITE and RHINE trials, which are identical, randomized double-masked studies compared the efficacy, durability, and safety of faricimab with aflibercept in patients with center-involving DME who were either treatment-naïve or received previous treatment with anti-VEGF therapy.
Patients were randomized 1:1:1 to faricimab 6.0 mg every 8 weeks (Q8W) after 6 initial every-4-week Q4W doses; faricimab 6.0 mg treated according to a personalized treatment interval (PTI) based on the treat-and-extend concept after 4 initial very-4-week doses; or aflibercept 2.0 mg every 8 weeks after 5 initial every-4-week doses.
The primary efficacy endpoint was the mean change in the best-corrected visual acuity (BCVA) from baseline averaged over study weeks 48, 52, and 56. The secondary endpoints were the proportion of patients with a 2-step or more improvement in the Early Treatment Diabetic Retinopathy Diabetic Retinopathy Severity Scale (ETDRS-DRSS) from baseline, the proportion of patients with a 15 or greater gain in ETDRS letters from baseline, the change in central subfield thickness (CST) from baseline, and the proportion of patients in the PTI arm receiving doses every 4, every 8, every 12, or every 16 weeks at 1 year.
Safety was assessed by the incidence and severity of ocular and nonocular adverse events.
The gains in the BCVA in the faricimab-treated patients were equivalent to (noninferior to) those achieved with aflibercept administered every 8 weeks.
At the 1-year time point, the faricimab patients dosed every 8 weeks and those in the PTI are had letter gains of 11.8 and 10.8 compared with aflibercept with a gain of 10.3 letters.
Wells reported that strong durability with faricimab was seen, i.e., more than 70% of patients achieved every-12-week or better dosing status at week 52--73.8% in the YOSEMITE study and 71.1% in the RHINE study with every 12-week and every-16-week dosing.
Regarding the CST, the change from baseline over 1 year of treatment, which was a mean decrease of almost 200 μm, consistently favored faricimab.
More faricimab-treated patients in the YOSEMITE study had a 2-step or more improvement in the DRSS by 1 year. In the RHINE study, the rates of improvement were similar among the 3 groups.
Faricimab had a good safety profile, with low rates of adverse effects. In addition, the rates of intraocular inflammation were low, with inflammation reported in 1.3% and 0.6%, respectively, of faricimab-treated and aflibercept-treated patients. No retinal vasculitis was reported in either study.
Wells also pointed out that more faricimab-treated patients had no DME through week 56 compared with aflibercept-treated patients.
The YOSEMITE and RHINE studies will continue for another year and will be followed by the RHONE-X long-term extension trial that ultimate will report 4-year data.
This article is adapted from Wells’ presentation at the Association for Research in Vision and Ophthalmology’s 2021 virtual annual meeting. He is a consultant to Roche.