Study dispels potential immunogenicity concerns regarding ranibizumab biosimilar
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A post hoc analysis of phase 3 trial data showed no association of immunogenicity with efficacy or safety for both ranibizumab and the biosimilar SB11 in patients with neovascular age-related macular degeneration.
In addition, a low incidence of antidrug antibodies was found with both drugs.
Byooviz (SB11, ranibizumab-nuna, Samsung Bioepis) was approved by the European Medicines Agency and the FDA in 2021 following a head-to-head phase 3 trial that demonstrated equivalent efficacy to the originator biologic Lucentis (ranibizumab, Genentech). In the current analysis, the association of immunogenicity to both ranibizumab products with efficacy, safety and pharmacokinetics was examined in 705 participants randomly assigned to receive either SB11 or ranibizumab.
No significant differences were reported in the immune responses of patients in the two groups. Production of antidrug antibodies (ADAs) was found in 14 of 330 participants (4.2%) in the SB11 group and 18 of 327 participants (5.5%) in the ranibizumab group.
Changes in best corrected visual acuity letter score from baseline to week 8 showed no differences between ADA-positive participants and ADA-negative participants. Similarly, central subfield thickness (CST) changes at week 4 did not differ between ADA-positive and ADA-negative participants. If differences in BCVA and CST were found from baseline to week 52, they were not associated with overall ADA status.
Drug-related intraocular inflammation adverse events occurred in one of 32 ADA-positive participants (3.1%) by week 52 and resolved after treatment with topical corticosteroids. In the ADA-negative group, four of 620 participants (0.6%) experienced at least one intraocular inflammation adverse event.
A slightly lower serum ranibizumab concentration in overall ADA-positive participants compared with ADA-negative participants was not considered to be clinically relevant.
“These findings suggest that particular concerns about immunogenicity and overall safety of this anti-VEGF biosimilar that will be used to treat retinal diseases do not appear warranted at this time, although routine pharmacovigilance monitoring remains warranted,” the study authors wrote.
Perspective
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The study by Bressler and colleagues examined an important aspect of ranibizumab, which is the impact of immunogenicity on safety and efficacy. It was studied in both biosimilar ranibizumab (SB11, Samsung Bioepis) and the innovator ranibizumab (Lucentis, Genentech). The study was based on the post hoc analysis of a randomized, double-masked, parallel-group, multicenter, phase 3 equivalence trial that examined the association between immunogenicity and pharmacokinetics, efficacy and safety profiles of the two ranibizumab products. Key criteria of immunogenicity assessment were analysis of serum anti-drug antibodies (ADA) at the end of 52 weeks after monthly injection of ranibizumab. Assessment of best corrected visual acuity and central foveal thickness as a marker of efficacy and intraocular inflammation as a sign of safety was done between ADA-positive and ADA-negative patients. It was concluded that immunogenicity was not associated with the efficacy and safety of both ranibizumab products. Furthermore, both products had overall low rates of ADA positivity, including neutralizing antibodies.
From the recent Bio-USER Survey by the International Retina Biosimilar Study Group regarding awareness of retina physicians practicing in the U.S. and Europe, we have learned that the majority of us have safety concerns related to biosimilars. Results of the study by Bressler and colleagues might be helpful in assurance about the safety of SB11, which is now available for clinical use as ranibizumab-nuna (Byooviz, Samsung Bioepis, Biogen) in cases of neovascular age-related macular degeneration. The overall low incidence of ADA with ranibizumab can alleviate the concerns of clinicians with biosimilar ranibizumab in terms of potentially significant adverse events such as blindness due to retinal vasculitis, which was seen with brolucizumab with high preexisting and induced ADA leading to immune complex formation.
As mentioned by the authors, as the data of ADA patients and pharmacokinetics measurements were low in number, robust statistical analysis was not possible. Furthermore, data from both innovator ranibizumab and biosimilar ranibizumab were pooled together probably due to lower numbers in each arm. A separate analysis would have been more meaningful. Overall, rather than in vitro findings, retinal physicians are looking for more information and for the real-world data of biosimilars as revealed by the Bio-USER Survey.
References:
- Sharma A, et al. Expert Opin Biol Ther. 2023;doi:10.1080/14712598.2023.2176218.
- Sharma A, et al. Eye (Lond). 2020;doi:10.1038/s41433-020-0853-9.
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