Efficacy of Faricimab versus Aflibercept in Diabetic Macular Edema in the 20/50 or Worse Vision Subgroup in Phase III YOSEMITE and RHINE Trials

Ophthalmology. 2024 Nov;131(11):1258-1270. doi: 10.1016/j.ophtha.2024.05.025. Epub 2024 Jun 8.

Abstract

Purpose: Diabetic Retinopathy Clinical Research Network Protocol T suggests that the response to treatment among patients with diabetic macular edema (DME) may vary depending on baseline best-corrected visual acuity (BCVA). We evaluated the efficacy of faricimab 6 mg versus aflibercept 2 mg over 2 years in patients with DME and baseline BCVA of 20/50 or worse enrolled in faricimab phase III trials.

Design: YOSEMITE and RHINE were identically designed, multicenter, randomized, double-masked, active comparator-controlled, noninferiority trials.

Participants: Adults ≥18 years of age with center-involving macular edema secondary to type 1 or 2 diabetes.

Methods: Patients were randomized to faricimab every 8 weeks (Q8W), faricimab personalized treat-and-extend (T&E) regimen, or aflibercept Q8W. Post hoc subgroup analyses were conducted using the intention-to-treat population with baseline BCVA of 20/50 or worse.

Main outcome measures: Changes in ETDRS BCVA and central subfield thickness (CST) from baseline to years 1 and 2 were compared between treatment arms using mixed-model repeated measures analyses.

Results: In YOSEMITE and RHINE, respectively, 220 and 217 patients in the faricimab Q8W arm, 220 and 219 patients in the faricimab T&E arm, and 219 and 214 patients in the aflibercept Q8W arm showed baseline BCVA of 20/50 or worse. In both trials, mean change in ETDRS BCVA was comparable between treatments across trials at years 1 and 2. In YOSEMITE, adjusted mean change from baseline in CST (μm) at year 1 was greater with faricimab Q8W (-232.8; P < 0.0001) and faricimab T&E (-217.4; P = 0.0004) ) versus aflibercept Q8W (-190.4). In RHINE, this was faricimab Q8W (-214.2; P = 0.0006) and faricimab T&E (-206.6; P = 0.0116) versus aflibercept Q8W (-186.6). In both trials, change from baseline in CST at year 2 was greater with faricimab Q8W versus aflibercept. The median time to first CST of <325 μm and first absence of intraretinal fluid was shorter in the faricimab arms versus the aflibercept arm, with fewer injections on average.

Conclusions: In patients with DME and baseline ETDRS BCVA of 20/50 or worse, faricimab treatment resulted in comparable visual acuity, greater reduction in retinal thickness, and fewer injections compared with aflibercept.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords: Aflibercept; Diabetic retinopathy; Faricimab; Retinal thickness; Visual acuity.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Comparative Study

MeSH terms

  • Aged
  • Angiogenesis Inhibitors* / administration & dosage
  • Angiogenesis Inhibitors* / therapeutic use
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Diabetic Retinopathy* / complications
  • Diabetic Retinopathy* / diagnosis
  • Diabetic Retinopathy* / drug therapy
  • Diabetic Retinopathy* / physiopathology
  • Double-Blind Method
  • Female
  • Humans
  • Intravitreal Injections*
  • Macular Edema* / diagnosis
  • Macular Edema* / drug therapy
  • Macular Edema* / etiology
  • Macular Edema* / physiopathology
  • Male
  • Middle Aged
  • Receptors, Vascular Endothelial Growth Factor* / administration & dosage
  • Receptors, Vascular Endothelial Growth Factor* / therapeutic use
  • Recombinant Fusion Proteins* / administration & dosage
  • Recombinant Fusion Proteins* / therapeutic use
  • Tomography, Optical Coherence
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Visual Acuity* / physiology

Substances

  • Recombinant Fusion Proteins
  • aflibercept
  • Receptors, Vascular Endothelial Growth Factor
  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factor A
  • Antibodies, Monoclonal, Humanized
  • VEGFA protein, human