Varied Faricimab Dosing Regimens Non-Inferior to Aflibercept in Patients with DME

Findings from YOSEMITE and RHINE show a significant rate of patients on faricimab were able to extend their dosing to once every 16 weeks after a year of therapy.

Faricimab administered once every 8 weeks following 6 doses administered once every 4 weeks provided noninferior benefit to aflibercept (EYLEA) administered once every 8 weeks, according to 1-year findings from the phase 3 YOSEMITE and RHINE trials.

The comparative trial data, presented at the American Society of Retina Specialists (ASRS) 2021 Scientific Meeting this weekend, support the novel bispecific antibody’s benefit in improving long-term vision gains relative to aflibercept in patients with diabetic macular edema.

Presented by Caroline Baumal, MD, a Professor at Tufts Medical Center, the RHINE and YOSEMITE trials observed the efficacy, safety, and durability of intravitreal faricimab versus aflibercept in treating DME. The investigative agent is a dual angiopoietin (Ang)-2 and VEGF-A inhibitor designed to reduce vascular leakage and inflammation while promoting vascular stability beyond anti-VEGF monotherapy in patients with DME.

The pair of phase 3 trials are double-masked, 100-week active comparator-controlled studies that randomized patients 1:1:1 to any of these doses:

  • Six doses of faricimab 6 mg once every 4 weeks, then 1 dose every 8 weeks (Q8W)
  • Four doses of faricimab 6 mg once every 4 weeks, then regular doses per personalized treatment interval (PTI)
  • 5 doses of aflibercept 2 mg once every 4 weeks, then 1 dose every 8 weeks

The PTI algorithm used by investigators is a regimen informed by treat-and-extend anti-VEGF dosing strategies, with intervals adjusted based on patient central subfield thickness (CST) and best corrected visual acuity (BCVA) changes at dosing visits.

Baumal and colleagues sought a primary endpoint of mean BCVA change from baseline at 1 year, averaged over weeks 48, 52, and 56. Their patient population included 1891 patients enrolled in either YOSEMITE (n = 940) or RHINE (n = 951).

Investigators observed a mean 1-year BCVA improvement of 10.7 and 11.8 letters in faricimab Q8W patients in YOSEMITE and RHINE, respectively, as well as improvements of 11.6 and 10.8 letters in faricimab PTI patients—indicating noninferior efficacy to aflibercept (10.9 and 10.3 letters, respectively).

Among patients who were treatment-naïve at baseline, 1-year BCVA improvements were consistent with the intent-to-treat population; no faricimab arm showed superiority to the aflibercept arm.

Patients administered either dose regimen of faricimab reported consistenly improved changed in CST and absence of intraretinal fluid over 1 year versus patients administered aflibercept.

More than half the faricimab PTI patients in YOSEMITE (52.8%) and RHINE (51.0%) achieved once every 16-week dosing at week 52; another 73.8% and 71.1%, respectively, achieved at least once every 12-week dosing by the time.

Investigators observed consistent tolerability with faricimab, with low intraocular inflammation rates and no cases of vasculitis nor occlusive retinitis.

“Faricimab administered Q8W or per PTI up to Q16W offered noninferior vision gains compared with aflibercept Q8W, while demonstrating improvements in anatomic endpoints and the potential for extended (up to Q16W) dosing at 1 year,” investigators concluded.

The study, “Efficacy, Safety, and Durability of Faricimab in Diabetic Macular Edema (DME): One-Year Results From the Phase 3 YOSEMITE and RHINE Trials,” was presented at ASRS 2021.