86-OR: Primary Results from Two Phase 3 Trials of Faricimab for Diabetic Macular Edema (DME): YOSEMITE and RHINE

Abstract

The leading cause of vision loss in people with diabetic retinopathy (DR) is DME. Intravitreal anti-VEGF therapy is the standard of care for DME; however, optimal vision outcomes are difficult to achieve, and the need for ongoing, often monthly injections is burdensome for patients, caregivers, and the health care system. Upregulation of both VEGF-A and angiopoietin-2 has been shown to synergistically induce vascular destabilization characteristic of DME; therefore, dual inhibition with faricimab, the first bispecific antibody designed for intraocular use, may improve outcomes beyond anti-VEGF monotherapy. YOSEMITE (NCT03622580) and RHINE (NCT03622593) are identical, randomized, phase 3 trials to assess the efficacy, durability, and safety of faricimab in DME. Patients 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 adjusted based on treatment response using prespecified vision and anatomic criteria. Safety and efficacy will be assessed Q4W through week 100. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Secondary endpoints included changes in anatomic outcomes over time, such as DR severity and central subfield thickness; and the proportion of patients on Q4W, Q8W, Q12W, or Q16W PTI dosing at 1 year. Safety endpoints were the incidence and severity of adverse events. Both studies met their primary endpoint and showed that faricimab dosed Q8W or per PTI demonstrated non-inferior visual acuity gains compared to aflibercept Q8W. More than half of all patients in the faricimab PTI arms had extended time between treatments to 16 weeks at 1 year - the first time this level of durability has been achieved in a phase 3 DME study. Faricimab was generally well-tolerated, with no new safety signals identified. Disclosure A. Hu: Advisory Panel; Self; Roche Pharma. J. R. Willis: Employee; Self; Genentech, Inc., Stock/Shareholder; Self; Roche Pharma. Z. Haskova: Employee; Self; Genentech, Inc. D. Silverman: Employee; Self; Roche Pharma. J. Ives: Employee; Self; Roche Pharma. K. Basu: Employee; Self; Genentech, Inc., Roche Pharma, Stock/Shareholder; Self; Genentech, Inc., Roche Pharma. H. Lin: Employee; Self; Genentech, Inc., Employee; Spouse/Partner; Genentech, Inc. Funding F. Hoffmann-La Roche, Ltd.