After 2 years, the improvements in vision and anatomy were sustained with extended dosing out to every 16 weeks in a high percentage of patients.
The results of the YOSEMITE and RHINE phase 3 trials that evaluated the efficacy of faricimab (Vabysmo, Genentech) for treating center-involved diabetic macular edema (DME) compared with aflibercept (Eylea, Regeneron Pharmaceuticals) found that after 2 years, the improvements in vision and anatomy were sustained with extended dosing out to every 16 weeks in a high percentage of patients.
Faricimab is the first bispecific antibody designed for intraocular use that blocks 2 pathways, the angiopoietin-2 (Ang-2) and the vascular endothelial growth factor (VEGF) A pathways.
The 1-year results from the 2 phase 3 clinical trials showed that this treatment promoted vascular stability and durability better than the current VEGF therapies for DME.
John A. Wells, III, MD, reported the 2-year results at the Angiogenesis, Exudation, and Degeneration 2022 virtual meeting. He is from the Chairman, Department of Ophthalmology, Palmetto Retina Center, Columbia, SC.
YOSEMITE and RHINE studies
In these trials, patients were randomized to either 2 regimens of faricimab, that is, 6.0 mg administered every 8 weeks following 6 initial loading doses every 4 weeks or a personalized treatment interval with 6.0 mg of faricimab after 4 initial loading doses every 4 weeks, or aflibercept (Eylea, Regeneron Pharmaceuticals) 2.0 mg administered every 8 weeks after 5 initial loading doses every 4 weeks. The YOSEMITE Study included 940 patients and RHINE 951 patients. The vast majority of patients completed the studies.
The primary end point was the mean change in the best-corrected visual acuity (BCVA) at 1 year, which was average with the 48-, 52-, and 56-week visits.
The personalized treatment interval is a treat-and-extend regimen that considers the changes in the central subfield thickness (CST) and the BCVA. After the initiation phase, every-4-week dosing was maintained until the CST decreased below 325 microns. When the CST stabilized the treatment interval could be extended by up to 4 weeks as long as the vision was stable; if the CST worsened the treatment could be adjusted depending on the severity of the worsening.
Continuation of results into year 2
Wells reported, “The vision gains with faricimab were noninferior to those achieved with aflibercept up to 1 year. All study arms gained about 10 to 11 letters at 1 year. These improvements were sustained through the second year and both faricimab arms were noninferior to aflibercept.”
At 1 year, over 50% of eyes in the personalized treatment arm were on an every-16-week dosing interval and another 20% were on an every-12-week dosing interval. Only 7% required monthly dosing for the entire year.
In year 2, the durability signals increased, with 60% to 65% on an every-16-week dosing interval and almost 80% of eyes were on an every-12-week dosing interval or longer.
The patients receiving personalized treatment received a median of 3 injections compared with 5 injections in the other 2 study arms.
Most of the patients who achieved an every-16 or every-12-week dosing interval with faricimab in year 1 maintained that level in the second year.
The gains in vision of 3 or more lines were comparable among the 3 arms through 2 years. Very few patients lost 3 or more lines of vision over the study course.
The decreases in the CST were substantial and sustained in all arms at 1 year. However, the faricimab-treated eyes had greater reductions at 1 year compared with aflibercept; the difference between the 2 drugs closed during the second year.
“The absence of DME, defined as a CST of less than 325 microns, occurred earlier and in more patients with faricimab compared with aflibercept through 2 years. In addition, more faricimab-treated eyes had no intraretinal fluid compared with aflibercept at 2 years,” he reported.
The investigators saw a trend toward more eyes treated with faricimab every 8 weeks having a 2-step or greater decrease in the Diabetic Retinopathy Severity Score compared with the other arms through 2 years.
No significant ocular or systemic safety signals were seen in the faricimab groups. The rates of ocular adverse events were low and similar in the 3 groups. In addition, low and similar rates of intraocular inflammation were seen in the 3 groups; no cases of retinal vasculitis occurred in any eyes. A few retinal and arterial occlusive events occurred that were not association with inflammation.
“Faricimab targets VEGF-A and Ang-2 to promote vascular stability. Comparable 1-year VA gains were seen with faricimab even up to every 16 weeks of dosing compared with aflibercept that were maintained through year 2. Almost 80% of eyes were on every-12-week dosing and almost 62% on every-16-week dosing in the personalized treatment arm through 2 years. Improved anatomic outcomes were seen with faricimab despite less treatment in the second year. No safety signals were seen,” Wells concluded.
The extension study is ongoing.