Efficacy and Safety of a Proposed Ranibizumab Biosimilar Product vs a Reference Ranibizumab Product for Patients With Neovascular Age-Related Macular Degeneration A Randomized Clinical Trial
Abstrakt
QUESTION Does SB11, a proposed ranibizumab biosimilar product, have equivalent best-corrected visual acuity (BCVA) and optical coherence tomography central subfield thickness (CST) outcomes and a similar safety profile to the reference ranibizumab product in patients with neovascular age-related macular degeneration? FINDINGS This randomized clinical equivalence trial found that SB11 demonstrated equivalence in efficacy for both primary end points: adjusted treatment differences between groups were within predefined equivalence margins for mean changes from baseline in both BCVA at week 8 and CST at week 4. Safety and immunogenicity profiles were similar between SB11 and ranibizumab.
MEANING These results indicate that SB11 is similar to its reference product, ranibizumab. This randomized clinical trial compares the efficacy, safety, and immunogenicity of SB11, a ranibizumab biosimilar product, with that of the reference ranibizumab for patients with neovascular age-related macular degeneration (AMD).
IMPORTANCE Neovascular age-related macular degeneration is the leading cause of blindness in individuals 50 years or older. The availability of a ranibizumab biosimilar product (SB11) may facilitate access to an effective alternative to this treatment.
OBJECTIVE To demonstrate equivalence of efficacy, similar safety, and similar immunogenicity of SB11 compared with the reference ranibizumab. DESIGN, SETTING, AND PARTICIPANTS This randomized, double-masked, parallel-group phase 3 equivalence study was conducted in 75 centers in 9 countries from March 14, 2018, to December 9, 2019, among 705 participants 50 years or older with neovascular age-related macular degeneration with active subfoveal choroidal neovascularization lesions.
Analysis was performed on an intent-to-treat basis. INTERVENTIONS Intravitreous injection of SB11 or ranibizumab, 0.5 mg, every 4 weeks through week 48.
MAIN OUTCOMES AND MEASURES Preplanned interim analysis after all participants completed the week 24 assessment of primary efficacy end points at week 8 for change from baseline in best-corrected visual acuity (BCVA) and week 4 for central subfield thickness (CST), with predefined equivalence margins for adjusted treatment differences of -3 letters to 3 letters for BCVA and -36 mu m to 36 mu m for CST. RESULTS Baseline and disease characteristics among 705 randomized participants (403 women [57.2%]; mean [SD] age, 74.1 [8.5] years) were comparable between treatment groups (SB11, 351; ranibizumab, 354).
Least-squares mean (SE) changes in BCVA from baseline at week 8 were 6.2 (0.5) letters in the SB11 group vs 7.0 (0.5) letters in the ranibizumab group, with an adjusted treatment difference of -0.8 letter (90% CI, -1.8 to 0.2 letters). Least-squares mean (SE) changes in CST from baseline at week 4 were -108 (5) mu m in the SB11 group vs -100 (5) mu m in the ranibizumab group, with an adjusted treatment difference of -8 mu m (95% CI, -19 to 3 mu m).
Incidences of treatment-emergent adverse events (231 of 350 [66.0%] vs 237 of 354 [66.9%]), including serious treatment-emergent adverse events (44 of 350 [12.6%] vs 44 of 354 [12.4%]) and treatment-emergent adverse events leading to study drug discontinuation (8 of 350 [2.3%] vs 5 of 354 [1.4%]), were similar in the SB11 and ranibizumab groups. Immunogenicity was low, with a cumulative incidence of antidrug antibodies up to week 24 of 3.0% (10 of 330) in the SB11 group and 3.1% (10 of 327) in the ranibizumab group.
CONCLUSIONS AND RELEVANCE These findings of equivalent efficacy and similar safety and immunogenicity profiles compared with ranibizumab support the use of SB11 for patients with neovascular age-related macular degeneration.