Review Shows Consistent Efficacy Between Ranibizumab Biosimilar, Reference Product

Netan Choudhry, MD

Credit: LinkedIn

A systematic review of 4 randomized controlled trials (RCTs) showed no significant differences in visual and anatomical outcomes between biosimilar ranibizumab and the reference product in the treatment of neovascular age-related macular degeneration (nAMD).¹

In addition, a meta-analysis of safety outcomes did not reveal significant differences when considering the reference anti-vascular endothelial growth factor (anti-VEGF) therapy and the studied biosimilars, including FYB201, SB11, RanizuRel, and Lupin’s biosimilar ranibizumab.

“Our findings were consistent with previously published retrospective studies and reviews and further expand on the bioequivalence of the 4 studied ranibizumab biosimilars,” wrote the investigative team, led by Netan Choudhry, MD, from Vitreous Retina Macula Specialists of Toronto.

Both patients and healthcare systems can experience a substantial burden with anti-VEGF treatment for nAMD, due to medication cost, time burden, and overall decrease in patient quality of life because of stress and anxiety. The introduction of biosimilars has been shown to reduce costs and improve access to safe and effective biological medicines. As the patent for ranibizumab expired in 2020 in the US, and in 2022 in Europe, ranibizumab biosimilars have been introduced into the market.

With a lack of fixed international guidelines for biosimilar approval, guidelines can differ between countries and may change with time. As a result, Choudhry and colleagues looked to address variability in medication development and the lack of unified approval guidelines. The systematic review and meta-analysis aimed to provide a comprehensive summary of the efficacy and safety of ranibizumab biosimilar therapies relative to the reference therapy for nAMD treatment.

Investigators conducted searches from January 2003 - August 2022 on Ovid MEDLINE, EMBASE, and the Cochrane Controlled Register of Trials. The team included RCTs reporting changes in best-corrected visual acuity (BCVA) reported in Early Treatment Diabetic Retinopathy Study (ETDRS) letters, the number of patients who lost or gained ≥15 letters in BCVA from baseline, changes in retinal thickness, and adverse events between treatment arms.

Excluded studies did not report visual outcomes following biosimilar and reference ranibizumab intravitreal injections, study arms combining anti-VEGF therapies with laser or steroid injections, sham injections as a control comparator, studies without English full texts, and non-comparative, observational study design.

A total of 16,712 studies underwent title and abstract screening, with 30 of these undergoing full-text screening to assess eligibility. Of these 30 studies, 5 studies that reported on 4 RCTS with a total of 1544 eyes at baseline were included in the systematic review and meta-analysis. Of the biosimilars used, FYB201 is under Biologics License Application review by the US Food and Drug Administration (FDA), SB11 is approved by the US FDA in 2021, RanizuRel was approved by DGCI in 2020, and Lupin’s ranibizumab is in phase 3 trial.²

Upon analysis, Choudhry and colleagues observed no significant difference between reference ranibizumab and any ranibizumab biosimilar medication included in the study for visual and anatomical outcomes.¹ The systematic review showed no obvious differences in measures of retinal thickness (central subfield thickness [CST] or central macular thickness [CMT] or change in BCVA between treatment groups.

When examining adverse events, the investigative team found no significant difference in treatment-emergent adverse events between ranibizumab biosimilar and reference ranibizumab groups in all 4 RCTS (risk ratio [RR], 1.06; 95% CI, 0.91 - 1.23; P = .45; I2 = 52%). In addition, the team observed no significant difference in intraocular pressure-related adverse events with significant heterogeneity (RR, 2.59; 95% CI, 0.11 - 62.25; P = .56; I2 = 76%).

“These analyses provide clinical context for alternatives to ranibizumab for nAMD as they begin to be used commercially,” investigators wrote. “Continued investigations of this topic with increased sample sizes are warranted to further characterize the safety and efficacy of anti-VEGF biosimilars.”

References

1. Hatamnejad A, Dadak R, Orr S, Wykoff C, Choudhry N. Systematic review of efficacy and meta-analysis of safety of ranibizumab biosimilars relative to reference ranibizumab anti-VEGF therapy for NAMD treatment. BMJ Open Ophthalmology. 2023;8(1). doi:10.1136/bmjophth-2022-001205
2. Kapur M, Nirula S, Naik MP. Future of anti-VEGF: Biosimilars and Biobetters. Int J Retina Vitreous 2022;8:2. doi:10.1186/s40942-021-00343-3pmid:34983660PubMedGoogle