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.


Conclusion

“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

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Frank G. Holz, MD
e:frank.holz@ukbonn.de
Holz receives research grants from Bioeq/Formycon, as well as research grants and honoraria for consultancy from Roche/Genentech and Novartis.