TY - JOUR
T1 - Efficacy and Safety of a Proposed Ranibizumab Biosimilar Product vs a Reference Ranibizumab Product for Patients with Neovascular Age-Related Macular Degeneration
T2 - A Randomized Clinical Trial
AU - Woo, Se Joon
AU - Veith, Miroslav
AU - Hamouz, Jan
AU - Ernest, Jan
AU - Zalewski, Dominik
AU - Studnička, Jan
AU - Vajas, Attila
AU - Papp, Andras
AU - Gabor, Vogt
AU - Luu, James
AU - Matuskova, Veronika
AU - Yoon, Young Hee
AU - Pregun, Tamás
AU - Kim, Taehyung
AU - Shin, Donghoon
AU - Bressler, Neil M.
N1 - Funding Information:
of the study was funded by Samsung Bioepis, Incheon, Republic of Korea.
Funding Information:
serving as a consultant for Samsung Bioepis and Panolos Bioscience; being cofounder of Retimark; serving as an advisory board member of Novartis and Novelty Nobility; receiving grants and personal fees from Samsung Bioepis, Novartis, Novelty Nobility, Alteogen, Kookje, and Curacle; and receiving lecture fees from Novartis, Bayer, Allergan, AbbVie, Alcon, Taejoon, SCAI Therapeutics, and Alteogen. Dr Studnička reported serving as a consultant for Bayer and Zeiss; receiving grants from Samsung Bioepis; and receiving lecture fees from Bayer. Dr Vajas reported receiving grants from Novartis, Bayer, Ophthotech/ Iveric Bio, Samsung Bioepis, Amgen, Qilu, Chengdu Kanghong, Roche, Mylan, Receptos, Shire, Panoptica, Xbrain, Formycon, Genentech, Bioeq, Allergan, Thrombogenics, Regeneron, Alcon, and Clearside Biomedical and serving as a consultant for and an advisory board member of Novartis, Bayer, Allergan, Bausch & Lomb, Medicontur, and Zeiss. Dr Papp reported serving as a consultant for Bayer and Novartis and receiving travel grants from Novartis; his company has received investigator fees from Samsung Bioepis, Roche, Iveric Bio, Allergan, and Chengdu Kanghong. Dr Gabor reported serving as a consultant for Alcon and Novartis and receiving travel grants from Novartis and Medicontur; his department has been involved in the conduct of several studies sponsored by Samsung Bioepis, Allergan, Chengdu Kanghong, Xbrane Biopharma, Thrombogenics, Amgen, Qilu, F. Hoffmann-La Roche, Bayer, Ophthotech, Novartis, and Regeneron. Dr Yoon reported serving as a consultant for Alcon, Allergan Bayer, and Roche; serving as a board member for Allergan, Bayer, and Roche; receiving grants from Allergan, Samsung Bioepis, Bayer, Novartis, and Roche; and receiving lecture fees from Allergan, Bayer, and Roche. Dr Pregun reported receiving travel grants from Alcon, Novartis, and Bausch & Lomb; his department has been involved in the conduct of several studies sponsored by Mylan, Samsung Bioepis, Xbrane Biopharma, Kanghong Pharmaceuticals, F. Hoffmann-La Roche, Allergan, Bayer, and Ophthotech. Dr Shin is an employee of Samsung Bioepis. Dr Bressler reported receiving grants from Samsung Bioepis to Johns Hopkins University during the conduct of the study and receiving grants from Bayer, Biogen, F. Hoffman-LaRoche, Novartis, and Regeneron outside the submitted work. No other disclosures were reported.
Publisher Copyright:
© 2021 American Medical Association. All rights reserved.
PY - 2021/1
Y1 - 2021/1
N2 - 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 μm to 36 μm 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) 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). 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. Trial Registration: ClinicalTrials.gov Identifier: NCT03150589.
AB - 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 μm to 36 μm 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) 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). 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. Trial Registration: ClinicalTrials.gov Identifier: NCT03150589.
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UR - http://www.scopus.com/inward/citedby.url?scp=85096668501&partnerID=8YFLogxK
U2 - 10.1001/jamaophthalmol.2020.5053
DO - 10.1001/jamaophthalmol.2020.5053
M3 - Article
C2 - 33211076
AN - SCOPUS:85096668501
SN - 2168-6165
VL - 139
SP - 68
EP - 76
JO - JAMA ophthalmology
JF - JAMA ophthalmology
IS - 1
ER -