Immunogenicity Not Associated with Safety Concerns of SB11, Ranibizumab for nAMD

SB11 and ranibizumab appeared to have comparable immunogenicity and safety profiles in a post-hoc analysis of a phase 3 equivalence trial.

New findings from a post-hoc analysis of a phase 3 equivalence trial suggest that immunogenicity was not associated with efficacy and safety of ranibizumab SB11 (Byooviz) and ranibizumab in trial participants with neovascular age-related macular degeneration (nAMD).

A clear association was not identified between overall ADA positivity and pharmacokinetics due to a low overall incidence of serum anti drug antibodies (ADAs).

“SB11 and ranibizumab appeared to have comparable immunogenicity and safety profiles, supporting previously published data regarding the safety and efficacy of SB11 in patients with nAMD,” wrote study author Se Joon Woo, MD, PhD, Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital.

Although biologics targeting vascular endothelial growth factor A (VEGF-A) are currently the main pharmaceutical treatment option for nAMD, they can incite immune responses against themselves and lead to the production of ADAs. SB11 and reference ranibizumab are monoclonal anti VEGF-A antibodies approved for treatment of nAMD and other retinal diseases.

Currently, the potential association of immunogenicity of ranibizumab products with treatment outcomes is unknown, making it warranted to further investigate potential safety concerns regarding immunogenicity. In a post-hoc analysis of the phase 3 equivalence trial, investigators examined the association between immunogenicity and pharmacokinetics (PK), efficacy, and safety profiles of the 2 ranibizumab products.

Study participants were randomly assigned 1:1 to receive intravitreal injections of either SB11 (0.5 mg) or ranibizumab (0.5 mg) every 4 weeks until week 48. Serum ADAs were analyzed during the study period until week 52 to measure immunogenicity.

These analyses were conducted on immunogenicity (overall ADA positivity) with best-corrected visual acuity (BCVA) and central subfield thickness (CST). Meanwhile, adverse events associated with intraocular inflammation (IOI) and serum ranibizumab levels were compared between overall ADA-positive and ADA-negative.

Of 1095 screen patients, a total of 705 study participants were randomly assigned to receive either SB11 (n = 351 [49.8%]) or RBZ (n = 354 [50.2%]) across 75 centers in 9 countries from March 2018 to December 2019.

The incidence of overall ADA-positive participants up to week 52 was similar, including 14 of 330 participants (4.2%) and 18 of 327 participants (5.5%) for the SB11 and ranibizumab groups, respectively. Thus, the overall incidence of ADA-positivity was 32 of 657 (4.9%) at week 52.

From baseline to week 52, the change in BCVA and CST were not associated with overall ADA status. The least-squares mean differences between overall ADA-positive and ADA-negative participants up to week 52 for BCVA and CST respectively, were 1.6 letters (95% CI, -2.7 to 5.8; P = .46) and 3 μm (95% CI, -23 to 29; P = .83).

The data show IOI-related adverse events occurred in 1 of 32 overall ADA-positive participants (3.1%) and 4 of 620 overall ADA-negative participants (0.6%). Investigators reported the mean serum ranibizumab concentrations over time were slightly lower in overall ADA-positive participants compared with the mean of ADA-negative participants, with a maximum value of 1389.3 pg/mL at week 16 vs. 1665.4 pg/mL at week 36, respectively.

“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,” Woo wrote.

The study, “Immunogenicity with Ranibizumab Biosimilar SB11 (Byooviz) and Reference Product Lucentis and Association with Efficacy, Safety, and Pharmacokinetics: A Post-Hoc Analysis of a Phase 3 Randomized Clinical Trial,” was published in JAMA Ophthalmology.