A phase 3 study for a biosimilar of ranibizumab for neovascular AMD has reported equivalent efficacy and similar safety for 705 nAMD patients.

A team of clinical researchers based at Johns Hopkins Hospital, Baltimore, Maryland, has reported findings of equivalent efficacy and similar safety and immunogenicity profiles with a biosimilar antibody for patients with neovascular age-related macular degeneration, compared to the reference product ranibizumab (Lucentis).  The biosimilar of the ranibizumab reference product, termed ”SBII”, was sponsored by Samsung Bioepis Co., Ltd., in association with Seoul National University Bundang Hospital, South Korea.  The results prepared a pre-planned interim analysis after all participants completed the week 24 assessment of primary efficacy with 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 μm to 36 μm for CST. The results of the study were commented by one of the co-authors, Dr. Neil Bressler of Johns Hopkins Hospital, who stated that, “the results showed equivalent efficacy for visual acuity outcomes at eight weeks and anatomic outcomes at four weeks, which were the endpoints required by the U.S. FDA (visual acuity) and the EMA (OCT central subfield thickness), respectively, to show equivalent efficacy for biosimilars to anti-VEGF agents used to treat nAMD.”


The results of the trial reported 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).  The 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) μm in the SB11 group vs −100 (5) μm in the ranibizumab group, with an adjusted treatment difference of −8 μm (95%CI, −19 to 3 μm).  Of significant interest by the clinical community, the 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. According to the researchers, 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. 


In summarising the data, the authors commented that “the generalizability of the results from this study is supported by its consistency with those of previous studies of ranibizumab. Specifically, mean changes from baseline inBCVA at week 24 were 9.3 letters compared with 6.5 letters in the MARINA study, 10.6 letters in the ANCHOR (Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in AMD) study, 6.6 letters in the CATT (Comparison of Age-Related Macular Degeneration Treatments Trials) study, and approximately 9 letters in the HARBOR (The Phase III, Double-Masked, Multicenter, Randomized, Active Treatment-Controlled Study of the Efficacy and Safety of 0.5 mg and 2.0 mg Ranibizumab Administered Monthly or on an As-Needed Basis [PRN] in Patients With Subfoveal Neovascular Age-Related Macular Degeneration) study.  In addition, mean changes from baseline in CST at week 24 were −100μm compared with approximately −160μm in the HARBOR study”.  While one limitation of the result was the relatively short duration over the 24-week period, it will be certainly interesting for observers to assess a similar profile by the end of the 48-week period.