Biosimilar medications have larger molecules and a more complex structure than generics, and originate from natural sources — thus the 30 or so that have already been approved by the US Food and Drug Administration (FDA) may create more clinician confidence to prescribe them, and patient affordability to both start treatment and continue it.
A biosimilar such as ranibizumab-nuna (SB11, Samsung Bioepis Co., Ltd./Biogen, Inc.) must prove as effective and safe as its reference drug, ranibizumab as well as demonstrate acceptable metabolization, and low stimulation of antidrug antibodies. So far, results with SB11 have been consistent with its reference, and now a longer-term phase III trial (NCT03150589) conducted at 75 centers in 9 countries demonstrates sound immunogenicity and pharmacokinetics, with data published in the British Journal of Ophthalmology.1 The FDA announced approval for ranibizumab-nuna on September 17, 2021.2
More than 700 patients 50 years of age or older with untreated subfoveal choroidal neovascularization (CNV) from neovascular age-related macular degeneration (nAMD) were randomized 1:1 for treatment with intravitreal injections of 0.5 mg SB11 or ranibizumab every 4 weeks between March 2018 and December 2019.1 Of these, 634 completed the 52-week clinical trial; 307 in the SB11 cohort, and 327 in the ranibizumab group. Patients and investigators were masked to group assignment.
Comparable results from baseline to week 52 were found for efficacy, safety, immunogenicity, and pharmacokinetics.1 Participants who received SB11 achieved improvement in best corrected visual acuity (BCVA) of least square mean (SE) 9.8 (0.8) letters, and those undergoing ranibizumab had an increase of 10.4 (0.7) letters. SB11 group members’ central subfield thickness (CST) changed by -140.0 (4.5) μm, and ranibizumab-treated individuals by -125.1 (4.3) μm. Patients in the SB11 group experienced a reduction in CNV size of -5.2 (0.3) mm2, and in the ranibizumab set at -4.6 (0.3) mm2.
The number of participants in each cohort with CNV leakage was proportionate during this investigation, as well as the percentage of patients with reduction of intraretinal or subretinal fluid. Mean scores in the National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) also improved in both groups, changing by 4.54 in the SB11 set, and 6.47 in the ranibizumab group. Adverse events, including treatment-emergent adverse events (TEAEs) were mostly mild to moderate and “not related to the study drug,” as well as similar between the two cohorts.1
Regarding immunogenicity, cumulative occurrence of antidrug antibodies was minor in each group; 4.2% for those receiving SB11 and 5.5% for ranibizumab-treated individuals — and antibodies were generally non-neutralizing. For pharmacokinetic analyses, 54 participants were chosen for pre- and post-injection serum samples to test drug concentration, with similar results in both cohorts. The study noted that pharmacokinetic analysis is limited because systemic absorption of intravitreally-administered drugs is unlikely, and vitreous fluid was not sampled in this trial.
“With SB11 and a number of other biosimilars under development, the availability of biosimilars may have a major role in ophthalmology, like the introduction of biosimilars (eg, SB2 as a biosimilar of infliximab) in other therapeutic areas,” investigators suggest.1
Disclosures: This study was funded by Samsung Bioepis Co., Ltd. Also, several of the study authors have declared affiliations with the biomedical and pharmaceutical industries. Please see the original reference for a full list of disclosures.
1. Bressler NM, Veith M, Hamouz J, et al. Biosimilar SB11 versus reference ranibizumab in neovascular age-related macular degeneration: 1-year phase III randomized clinical trial outcomes. Br J Ophthalmol. Published online October 16, 2021. doi:10.1136/bjophthalmol-2021-319637
2. FDA approves first biosimilar to treat macular degeneration disease and other eye conditions. FDA news release. FDA.gov. https://www.fda.gov/news-events/press-announcements/fda-approves-first-biosimilar-treat-macular-degeneration-disease-and-other-eye-conditions. Updated September 17, 2021. Accessed October 31, 2021.