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
Language English Country United States Media print
Document type Clinical Trial, Phase III, Comparative Study, Equivalence Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
PubMed
33211076
PubMed Central
PMC7677876
DOI
10.1001/jamaophthalmol.2020.5053
PII: 2772987
Knihovny.cz E-resources
- MeSH
- Biosimilar Pharmaceuticals adverse effects pharmacokinetics therapeutic use MeSH
- Time Factors MeSH
- Double-Blind Method MeSH
- Angiogenesis Inhibitors adverse effects pharmacokinetics therapeutic use MeSH
- Intravitreal Injections MeSH
- Middle Aged MeSH
- Humans MeSH
- Macular Degeneration diagnosis drug therapy physiopathology MeSH
- Choroidal Neovascularization diagnosis drug therapy physiopathology MeSH
- Recovery of Function MeSH
- Ranibizumab adverse effects pharmacokinetics therapeutic use MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Therapeutic Equivalency MeSH
- Vascular Endothelial Growth Factor A antagonists & inhibitors MeSH
- Treatment Outcome MeSH
- Vision, Ocular drug effects MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Equivalence Trial MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Biosimilar Pharmaceuticals MeSH
- Angiogenesis Inhibitors MeSH
- Ranibizumab MeSH
- Vascular Endothelial Growth Factor A MeSH
- VEGFA protein, human MeSH Browser
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.
Department of Ophthalmology 3rd Faculty of Medicine Charles University Prague Prague Czech Republic
Department of Ophthalmology Asan Medical Center University of Ulsan College of Medicine Seoul Korea
Department of Ophthalmology Bajcsy Zsilinszky Hospital Budapest Hungary
Department of Ophthalmology Central Military Hospital Prague Czech Republic
Department of Ophthalmology Medical Centre Hungarian Defence Forces Budapest Hungary
Department of Ophthalmology Semmelweis University Budapest Hungary
Department of Ophthalmology University Hospital Brno Brno Czech Republic
Department of Ophthalmology University Hospital Hradec Kralove Hradec Kralove Czech Republic
Department of Ophthalmology University Hospital Kralovske Vinohrady Prague Czech Republic
Department of Ophthalmology University of Debrecen Debrecen Hungary
Diagnostic and Microsurgery Center of the Eye LENS Olsztyn Poland
Faculty of Medicine Masaryk University Brno Czech Republic
Medical Team Samsung Bioepis Incheon Korea
Retina Consultants of Southern Colorado Colorado Springs
Wilmer Eye Institute Johns Hopkins University School of Medicine Baltimore Maryland
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ClinicalTrials.gov
NCT03150589
