Efficacy and Safety of Biosimilar FYB201 Compared with Ranibizumab in Neovascular Age-Related Macular Degeneration

Ophthalmology. 2022 Jan;129(1):54-63. doi: 10.1016/j.ophtha.2021.04.031. Epub 2021 May 3.


Purpose: This trial was conducted to investigate the clinical equivalence of the proposed biosimilar FYB201 and reference ranibizumab in patients with treatment-naive, subfoveal choroidal neovascularization caused by neovascular age-related macular degeneration (nAMD).

Design: This was a prospective, multicenter, evaluation-masked, parallel-group, 48-week, phase III randomized study.

Participants: A total of 477 patients were randomly assigned to receive FYB201 (n = 238) or reference ranibizumab (n = 239).

Methods: Patients received FYB201 or reference ranibizumab 0.5 mg by intravitreal (IVT) injection in the study eye every 4 weeks.

Main outcome measures: The primary end point was change from baseline in best-corrected visual acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 8 weeks before the third monthly IVT injection. Biosimilarity of FYB201 to its originator was assessed via a 2-sided equivalence test, with an equivalence margin in BCVA of 3 ETDRS letters.

Results: The BCVA improved in both groups, with a mean improvement of +5.1 (FYB201) and +5.6 (reference ranibizumab) ETDRS letters at week 8. The analysis of covariance (ANCOVA) least squares mean difference for the change from baseline between FYB201 and reference ranibizumab was -0.4 ETDRS letters with a 90% confidence interval (CI) of -1.6 to 0.9. Primary end point was met as the 90% CI was within the predefined equivalence margin. Adverse events were comparable between treatment groups.

Conclusions: FYB201 is biosimilar to reference ranibizumab in terms of clinical efficacy and ocular and systemic safety in the treatment of patients with nAMD.

Keywords: Biosimilar; FYB201; Lucentis; Neovascular age-related macular degeneration; Ranibizumab.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / pharmacokinetics
  • Angiogenesis Inhibitors / therapeutic use*
  • Biological Availability
  • Biosimilar Pharmaceuticals / pharmacokinetics
  • Biosimilar Pharmaceuticals / therapeutic use*
  • Choroidal Neovascularization / diagnosis
  • Choroidal Neovascularization / drug therapy*
  • Choroidal Neovascularization / metabolism
  • Choroidal Neovascularization / physiopathology
  • Double-Blind Method
  • Female
  • Fluorescein Angiography
  • Humans
  • Intravitreal Injections
  • Male
  • Middle Aged
  • Prospective Studies
  • Ranibizumab / pharmacokinetics
  • Ranibizumab / therapeutic use*
  • Therapeutic Equivalency
  • Tomography, Optical Coherence
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Visual Acuity / physiology
  • Wet Macular Degeneration / diagnosis
  • Wet Macular Degeneration / drug therapy*
  • Wet Macular Degeneration / metabolism
  • Wet Macular Degeneration / physiopathology


  • Angiogenesis Inhibitors
  • Biosimilar Pharmaceuticals
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Ranibizumab