A long-term follow-up of a phase 3 equivalence study comparing the ranibizumab biosimilar SB11 (Byooviz, Samsung Bioepis) to the reference product (Lucentis) in neovascular age-related macular degeneration (nAMD) found the similarity in efficacy endpoints reported at 4 and 8 weeks was maintained through 52 weeks.

The authors noted that nAMD is a leading cause of visual impairment and blindness in older adults, and intravitreal injections of vascular endothelial growth factor inhibitors, including ranibizumab, are the standard treatment for nAMD. These therapies are a “substantial economic burden” for patients, they said. Biosimilars could expand patient access and “reduce the socioeconomic burden of blindness caused by nAMD.”

Improvements in visual outcomes remained stable through 52 weeks

Patients were randomized to monthly intravitreal injections of biosimilar SB11 or the ranibizumab originator for one year. In the investigators’ original publication, equivalence between SB11 and the reference product was reported for the primary efficacy endpoints: change from baseline of optical coherence tomography central subfield thickness (CST) at week 4 and best-corrected visual acuity (BCVA) at week 8.

The current report described the efficacy, safety, and immunogenicity results for the 634 patients (n = 307 randomized to the biosimilar; n = 327 to the reference product) who completed the study through the final visit at 52 weeks.

The authors said their final efficacy results demonstrated that the previously reported improvements “remained stable and appeared comparable between treatment groups at all time points up to week 52.” The adjusted treatment difference between the biosimilar and reference product for BCVA was -0.6 letters (90% CI, -2.1 to 0.9). For change in CST, the adjusted treatment difference was -14.9 µm (95% CI, -25.3 to -4.5).

Comparable Safety Immunogenicity, and Pharmacokinetic Profiles

The investigators described the safety profile of SB11 in this study as “consistent with the known [ranibizumab] profile,” with no new safety concerns identified. Treatment-emergent adverse events (TEAEs) were “mostly” mild or moderate in intensity, and the majority of AEs were not related to the study drugs.

Two percent of patients in the biosimilar group and 1.1% of patients in the originator group experienced ocular TEAEs leading to discontinuation of the study treatment, a difference that was not statistically significant. Intraocular inflammation in the SB11 group was “low” compared to reported rates with ranibizumab treatment, however, numerically higher than that in the originator group.

According to the authors, “a much larger number of study participants from a much larger case series would be needed to determine if these small numerical differences were due to chance or truly represented a small difference in ocular TEAEs.” An increase in intraocular pressure and conjunctival hemorrhage each occurred in more than 5% of the participants, with comparable percentages between groups.

The cumulative incidence of anti-drug antibodies (ADAs) over the 52-week study was 4.2% of patients receiving the biosimilar and 5.5% receiving the reference product. There were no significant differences in the incidences of ADAs or neutralizing antibodies between groups, and they were within the known range for ranibizumab, according to the investigators. TEAEs by ADA status were also similar between groups. Pharmacokinetic analysis of 54 patients showed “comparable” mean serum concentrations and pharmacokinetic profiles.

To the authors’ knowledge, their study is the first to report phase 3, 52-week follow-up data on the ranibizumab biosimilar SB11 for treating nAMD. They concluded based on their results that SB11 and the reference product have comparable efficacy, safety, immunogenicity, and pharmacokinetic profiles, and the similarity between ranibizumab products was maintained at all time points through week 52, “confirming the comparable longer-term efficacy” of SB11.

Source:- Center For Biosimilar