Immunogenicity to a ranibizumab biosimilar does not significantly impact treatment outcomes in patients with neovascular age-related macular degeneration (nAMD) and other retinal diseases, according to research published in JAMA Ophthalmology.
Investigators conducted a post hoc analysis of a randomized, double-masked, parallel-group phase 3 equivalence study to examine the association between immunogenicity to ranibizumab-nuna, previously called SB11, and reference ranibizumab. They also reviewed the efficacy, safety, and pharmacokinetics profiles in patients (≥50 years of age) with nAMD and active subfoveal choroidal neovascularization lesions.
The original multinational, multicenter study included participants from 75 centers in 9 countries and was conducted between March 14, 2018, and December 9, 2019 (ClinicalTrials.gov Identifier: NCT03150589). For that trial, patients were randomly assigned (1:1) to receive intravitreal injections of ranibizumab-nuna (0.5 mg) or ranibizumab (0.5 mg) every 4 weeks until week 48. The primary outcomes were change in best-corrected visual acuity (BCVA) from baseline to week 8 and change in central subfield thickness from baseline to week 4. Secondary outcomes included adverse events (AEs), serum concentrations of ranibizumab,and immunogenicity at various points up to week 52.
In the current study, the investigators compared BCVA, central subfield thickness, AEs associated with intraocular inflammation, and serum ranibizumab levels between ADA-positive and ADA-negative patients.
A total of 705 patients (mean age, 74.1 years; 57.2% women and 42.8% men) were included in the study, and of those, 634 completed 52 weeks of follow up. At week 52, the investigators found 4.9% of patients were ADA-positive and 95.1% of patients were ADA-negative.
The team reported no significant difference between ADA-positive and ADA-negative patients in the least-squares mean difference for BCVA (1.6±2.2 letters; 95% CI, -2.7 to 5.8; P=.46) nor for central subfield thickness (3±13 μm; 95% CI, -23 to 29; P=.83). They found intraocular inflammation-related AEs occurred in 3.1% of ADA-positive patients and 0.6% of ADA-negative patients.
The researchers did not perform formal statistical analysis on the pharmacokinetic data due to a low total number of ADA-positive patients in that dataset (3/54 patients). They noted the maximum serum ranibizumab concentration was 1389.3 pg/mL (at week 16) for ADA-positive participants and 1665.4 pg/mL (at week 36) in ADA-negative patients.
“Results suggest that the incidence of antidrug antibodies was low for ranibizumab products, and its immunogenicity did not seem to have a clinically relevant association with their efficacy, safety, or [pharmacokinetic] profiles,” the researchers report.
The primary limitation of the study was the small number of participants who developed ADA and/or neutralizing ADAs in the study period and of participants with pharmacokinetic measurements.
Disclosure: This research was supported by Samsung Bioepis. Multiple study authors declared affiliations with the biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Bressler NM, Kim T, Oh I, Russo P, Kim MY, Woo SJ. 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. Published online December 15, 2022. JAMA Ophthalmol. doi:10.1001/jamaophthalmol.2022.5403