As biosimilars become more and more available, companies are conducting clinical trials to prove their efficacy and bio equivalence for FDA approval. During the American Academy of Ophthalmology (AAO) 2022 Annual Meeting, three scientific abstracts relating to ophthalmology biosimilars from Biogen and Samsung Bioepis – ranibizumab and aflibercept – were presented as e-posters on demand. The three sets of data included: (1) SB15, a Proposed Biosimilar to Aflibercept, in Neovascular Age-Related Macular Degeneration (nAMD): 32-week Results; (2) Correlation Analysis between Immunogenicity and Clinical Outcomes of an Approved Ranibizumab Biosimilar, Byooviz™ (SB11); and (3) A Post Hoc Analysis of A Phase III Trial to Define Baseline Factors Associated with Treatment Outcomes of SB11 (Ranibizumab Biosimilar).
SB15: 32-Week Results
This was the first time Phase 3 data was presented for SB15, the aflibercept biosimilar candidate, which showed equivalent efficacy and comparable safety, immunogenicity, and pharmacokinetics profile to reference aflibercept in the Phase 3 study interim analysis. Samsung Bioepis noted that as with any biologic therapies, immunogenicity is an important risk factor that can impact clinical outcomes of treatment.
Additionally, there were no new safety signals identified and there were similar incidence and profile of TEAEs between SB15 and aflibercept. The incidence of overall ADA-positivity was low and comparable between SB15 and aflibercept.
The study involved 449 participants with treatment-naïve nAMD and BCVA of 20/40 to 20/200 (letter score of 73 to 34, inclusive). The participants were randomized 1:1 to intravitreal injection of 2mg SB15 or the reference drug, aflibercept, for 48 weeks. At Week 32, the participants in the reference aflibercept group were re-randomized 1:1 for acquiring switch data.
The final 56-week study results will be presented in the future, with additional long-term data addressing the biosimilarity of SB15 to aflibercept.
Correlation Analysis for SB11
While ranibizumab (RBZ) and other anti-VEGF agents commonly are used in the management of neovascular age-related macular degeneration (nAMD), all of these biologic products have the potential to induce the development of anti-drug antibodies (ADA). Samsung Bioepis notes that this might be concerning as ADA may neutralize the ranibizumab, thereby limiting its effectiveness.
In the correlation analysis, authors found that based on historical RBZ data, ADA were present in ~1%-9% of participants after a treatment period of 6-24 months compared with baseline values (pre-existing ADA) of ~0%-5%. The incidence of overall ADA-positive participants was low as 4.6% of 691 participants (4.2% in SB11 versus 5.5% in RBZ).
Additionally, baseline demographics and disease characteristics did not reveal any notable difference between overall ADA-positive and ADA-negative participants up to Week 52. The change from baseline in best-corrected visual acuity (BCVA) and central subfield thickness (CST) were not associated with ADA nor NAb status at Week 52.
However, a potential correlation between immunogenicity and pharmacokinetics profiles of SB11 and RBZ could not be excluded as mean serum ranibizumab concentrations were slightly lower in overall ADA-positive participants, when compared with ADA-negative participants.
Post-Hoc Analysis for SB11
The post-hoc analysis based on the Phase 3 study of SB11 confirmed its low immunogenicity profile and no correlation was found between immunogenicity and clinical outcomes.
The subgroup and ad hoc analysis of a randomized, double-masked, parallel-group, multicenter, 52-week phase 3 clinical trial was conducted in 75 centers across 9 countries. 705 participants were randomized 1:1 to receive every 4-week intravitreal injection of either SB11 or RBZ 0.5 mg for 48 weeks, following up to week 52.
Baseline age, best-corrected visual acuity (BCVA) and total lesion size were associated with mean change from baseline improvement in BCVA at week 52. Baseline age, BCVA and central subfield thickness (CST) were associated with reduction in mean change from baseline CST at week 52. Essentially, baseline age, BCVA, CST, and total lesion size were identified to be associated with 1 year visual and anatomical outcomes when treating neurovascular age-related macular degeneration with SB11 or rRBZ.
Biosimilars can expand markets for biologic drugs and reduce drug spending. The promise of biosimilars remains strong, despite their slow uptake in the US. The global demand for biosimilars is expanding over time and eventually will over take branded biologic drugs in the coming years.