• COVID-19
  • Biosimilars
  • Cataract Therapeutics
  • DME
  • Gene Therapy
  • Workplace
  • Ptosis
  • Optic Relief
  • Imaging
  • Geographic Atrophy
  • AMD
  • Presbyopia
  • Ocular Surface Disease
  • Practice Management
  • Pediatrics
  • Surgery
  • Therapeutics
  • Optometry
  • Retina
  • Cataract
  • Pharmacy
  • IOL
  • Dry Eye
  • Understanding Antibiotic Resistance
  • Refractive
  • Cornea
  • Glaucoma
  • OCT
  • Ocular Allergy
  • Clinical Diagnosis
  • Technology

Finding clinical equivalence of biosimilar, reference ranibizumab


Investigators find no clinically relevant differences in safety profiles.

This article was reviewed by Frank G. Holz, MD

FYB201 (Bioeq), a proposed biosimilar to ranibizumab, demonstrated similar clinical efficacy, safety, and immunogenicity as a treatment for newly diagnosed subfoveal neovascular age-related macular degeneration (AMD) compared with reference ranibizumab (Lucentis; Roche/Genentech), according to Frank G. Holz, MD.

Outcomes of patients treated with the reference ranibizumab and biosimilar were investigated in the prospective COLUMBUS-AMD trial (NCT02611778).

Related: PDS with ranibizumab signals paradigm shift in treatment of nAMD

Holz, who is professor and chair of the Department of Ophthalmology at the University of Bonn in Germany, presented the research at the American Academy of Ophthalmology’s virtual 2020 annual meeting.

“Biosimilars are less-expensive alternatives to reference biologic medicines,” Holz said. “To receive marketing approval, biosimilars need to undergo comprehensive studies demonstrating high similarity with the reference biologic in all critical quality attributes, including physical, chemical, and biological properties.”

COLUMBUS-AMD investigators examined the clinical equivalence of the biosimilar candidate FYB201 and reference ranibizumab, according to Holz.

“The findings of this study demonstrated the biosimilarity of FYB201 and reference ranibizumab with regard to efficacy, as well as safety,” he said. “This is in patients with newly diagnosed neovascular AMD. They suggest that FYB201 may offer a new, high-value treatment option for patients with neovascular AMD.”

COLUMBUS-AMD enrolled patients 50 years and older with subfoveal or juxtafoveal choroidal neovascularization (CNV) with foveal-involving leakage related to the CNV activity.

Eligible patients needed to have foveal center point (FCP) retinal thickness greater than or equal to 350 µm on spectral-domain optical coherence tomography, a total lesion area less than or equal to 12 MPS disc areas, total CNV area greater than or equal to 50% of total lesion area, and BCVA between 20/32 and 20/100 in the study eye.

Related: What a proposed biosimilar may mean for subfoveal wet AMD

Intravitreal injections

The patients were randomly assigned 1:1 to receive monthly intravitreal injections of FYB201 0.5 mg or reference ranibizumab 0.5 mg for up to 48 weeks.

The primary end point was change from baseline BCVA after 8 weeks.

Key secondary end points included change from baseline BCVA at 48 weeks and change from baseline FCP retinal thickness at 48 weeks, as well as safety and immunogenicity.

A total of 477 patients were randomly assigned to the 2 treatment arms. The 2 groups were well balanced at baseline with respect to median age (76 years), gender distribution (approximately 44% male), and distribution of BCVA.

The study met its primary end point, showing that the 90% CI for the change from baseline in Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA after 8 weeks was within the predefined equivalence margin.

Related: Choosing a syringe for intravitreal injection

The analysis of least squares mean change in BCVA showed improvements of 5.1 ETDRS letters in eyes treated with FYB201 and 5.4 ETDRS letters in eyes treated with reference ranibizumab.

The least squares mean difference between groups of study eyes was –0.4 ETDRS letters, with a 90% CI of –1.6 to 0.9 ETDRS letters. The predefined equivalence margin was –3.5 to 3.5 ETDRS letters.

At all follow-up visits, mean study eye BCVA and mean change from baseline in study eye FCP retinal thickness were highly similar between the groups of eyes treated with FYB201 and reference ranibizumab.

The overall safety profiles were also highly similar for the 2 study groups. Rates of any adverse event (AE), drug-related AEs, and serious drug-related AEs in the FYB201 group were 64.7%, 8.4%, and 1.3%, respectively; corresponding rates in the reference ranibizumab group were 69.9%, 10.5%, and 1.3%, respectively.

Related: Deep learning algorithm proving accurate for AMD classification

All-cause treatment-emergent intraocular inflammation occurred in 8.4% of eyes in both groups; the rate of treatment-emergent intraocular inflammation considered related to the investigational medicinal product was 0.8% in both groups.

The types of ocular AEs occurring in the 2 treatment groups were also similar, and most AEs in both groups were mild or moderate in severity.


“No clinically relevant differences in safety profiles were identified between treatment groups,” Holz said.

The immunogenicity analyses characterized the development of antidrug antibodies and neutralizing antibodies and showed that FYB201 and reference ranibizumab had comparable immunogenicity profiles.

The rate of antidrug antibody development was 5.9% in both treatment groups, and the ADA titers were also similar. A single patient in the FYB201 group developed neutralizing antibodies between weeks 24 and 48.

Read more by Cheryl Guttman Krader


Frank G. Holz, MD
Holz receives research grants from Bioeq/Formycon, as well as research grants and honoraria for consultancy from Roche/Genentech and Novartis.

Related Videos
EyeCon 2024: Peter J. McDonnell, MD, marvels on mentoring, modern technology, and ophthalmology’s future
EyeCon Co-chair Oluwatosin U. Smith, MD: Passion for Research and Education Drives Her Commitment to Ophthalmology
Video 3 - "Approaching Asymptomatic Cases with Risk Factors"
Video 2 - "Do Dry Eye Diagnostics Change the Management of Dry Eye?"
Dr. SriniVas Sadda Discusses Vision for ARVO as New President: Collaboration, Funding Challenges, and Impact of Annual Meetings
Deb Ristvedt, DO's CIME 2024 Talk Highlights Innovations in Treating Glaucoma via the Trabecular Meshwork
Dr. Inder Paul Singh's Insights: Improving Glaucoma Outcomes with Early Intervention and Reduced Medication
CIME 2024: Kelsey Roelofs, MD, details collaborative strategies for the management of thyroid eye disease
CIME 2024: Diagnostic tips and treatments for managing Demodex blepharitis
© 2024 MJH Life Sciences

All rights reserved.