Abstract
Purpose :
Diabetic macular edema (DME) is a multifactorial disease, and best-achievable visual responses to anti-VEGF monotherapy are difficult to achieve and maintain in clinical practice. Dual inhibition of angiopoietin-2 and VEGF-A with faricimab, the first bispecific antibody designed for intraocular use, may synergistically promote vascular stability and improve outcomes in DME. Herein we describe the design and rationale of the phase 3 YOSEMITE and RHINE trials, which assessed the safety, efficacy, and durability of faricimab in patients with DME.
Methods :
YOSEMITE (NCT03622580) and RHINE (NCT03622593) are identical, randomized, double-masked, active comparator–controlled, 100-week, phase 3 trials of faricimab in DME. Treatment-naïve or previously anti-VEGF–treated patients with center-involving DME were randomized 1:1:1 to faricimab 6.0 mg every 8 weeks (Q8W) after 6 initial Q4W doses; faricimab 6.0 mg per personalized treatment interval (PTI) after 4 initial Q4W doses; or aflibercept 2.0 mg Q8W after 5 initial Q4W doses. Dosing intervals in the PTI arm were determined by an automated algorithm, and could be reduced or extended by 4-week increments (from Q4W up to Q16W) according to prespecified BCVA and CST criteria at active dosing visits. The PTI algorithm is based on the treat-and-extend concept, and was designed to enable personalized therapy for DME, reduce injection frequency, and potentially optimize real-world outcomes.
Results :
Safety and efficacy were assessed Q4W through week 100. To account for differences in time from last treatment and BCVA variability, the primary efficacy endpoint was mean change in BCVA from baseline averaged over weeks 48, 52, and 56. Secondary endpoints included the proportion of patients with ≥ 2-step ETDRS-DRSS improvement at week 52, change in CST from baseline, and the proportion of patients in the PTI arm receiving Q4W, Q8W, Q12W, or Q16W dosing at 1 year. Safety outcomes included the incidence and severity of ocular and nonocular adverse events.
Conclusions :
YOSEMITE and RHINE were designed to evaluate whether dual inhibition of angiopoietin-2 and VEGF-A with faricimab may improve outcomes beyond anti-VEGF monotherapy in patients with DME. The PTI arm will examine the potential for individualized faricimab therapy, tailored according to patient needs, to reduce treatment burden while maintaining efficacy.
This is a 2021 ARVO Annual Meeting abstract.