Biosimilar SB11 versus reference ranibizumab in neovascular age-related macular degeneration: 1-year phase III randomised clinical trial outcomes

Abstract

Background/aims: To provide longer-term data on efficacy, safety, immunogenicity and pharmacokinetics (PK) of ranibizumab biosimilar SB11 compared with the reference ranibizumab (RBZ) in patients with neovascular age-related macular degeneration (nAMD).

Methods: Setting: Multicentre. Design: Randomised, double-masked, parallel-group, phase III equivalence study. Patient population: ≥50 years old participants with nAMD (n=705), one 'study eye'.

Intervention: 1:1 randomisation to monthly intravitreal injection of 0.5 mg SB11 or RBZ. Main outcome measures: Visual efficacy endpoints, safety, immunogenicity and PK up to 52 weeks.

Results: Baseline and disease characteristics were comparable between treatment groups. Of 705 randomised participants (SB11: n=351; RBZ: n=354), 634 participants (89.9%; SB11: n=307; RBZ: n=327) completed the study until week 52. Previously reported equivalence in primary efficacy remained stable up to week 52 and were comparable between SB11 and RBZ. The adjusted treatment difference between SB11 and RBZ in full analysis set at week 52 of change from baseline in best-corrected visual acuity was -0.6 letters (90% CI -2.1 to 0.9) and of change from baseline in central subfield thickness was -14.9 µm (95% CI -25.3 to -4.5). The incidence of ocular treatment-emergent adverse events (TEAEs) (SB11: 32.0% vs RBZ: 29.7%) and serious ocular TEAE (SB11: 2.9% vs RBZ: 2.3%) appeared comparable between treatment groups, and no new safety concerns were observed. The PK and immunogenicity profiles were comparable, with a 4.2% and 5.5% cumulative incidence of antidrug antibodies up to week 52 for SB11 and RBZ, respectively.

Conclusions: Longer-term results of this study further support the biosimilarity established between SB11 and RBZ.

Keywords: degeneration; macula; neovascularisation; retina.

Figure 1

CONSORT diagram of participants’ flow through the trial. (A) One participant was excluded from both full analysis set and safety set, because this participant was misrandomised and discontinued from the study before first dosing. (B) One participant was initially randomised to receive SB11 but incorrectly received the injection to the fellow eye, while RBZ was injected to the study eye until week 20 (Study day 141) of the study. This participant was discontinued from the study (Study day 164) primarily due to protocol deviation but later included in the RBZ treatment group in the safety set. IP, investigational product; RBZ, reference ranibizumab.

Figure 2

(A) Change from baseline in BCVA at each timepoint through week 52 in the full analysis set. Mean change±SE from baseline through week 52 in BCVA in the full analysis set. The table reports the number of participants per timepoint. The complete list of values and participants per timepoint is reported in online supplemental table 1. Mean (SD) change from baseline in BCVA for participants who completed week 52 of the study: SB11 (n=309), 9.7 (11.4) letters; RBZ (n=327), 10.4 (11.5) letters. Circles represent mean and error bars represent SE at each timepoint. (B) Change from baseline in CST at each timepoint through week 52 in the full analysis set. Mean change±SE from baseline through week 52 in CST in the FAS. The table reports the number of participants per timepoint. The complete list of values and participants per timepoint is reported in online supplemental table 2. Mean (SD) change from baseline in CST for participants who completed week 52 of the study: SB11 (n=308), –133.6 (103.9) μm; RBZ (n=327), –128.4 (116.1) μm. Circles represent mean and error bars represent SE at each timepoint. BCVA, best-corrected visual acuity (ETDRS letter score); CST, central subfield thickness; ETDRS, early treatment diabetic retinopathy study; RBZ, reference ranibizumab.