Research Article
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Year 2025, Volume: 16 Issue: 3, 352 - 361, 01.07.2025

Mehmet Orkun Sevik , Simge Gizem Koyu , Aslan Aykut , Didem Dizdar Yiğit , Özlem Şahin

https://doi.org/10.31067/acusaglik.1528212

Abstract

Project Number

Not applicable.

References

  • 1 Constable I, Shen WY and Rakoczy E. Emerging biological therapies for age-related macula degeneration. Expert Opin Biol Ther. 2005;5:1373-85. DOI:10.1517/14712598.5.10.1373
  • 2 Sharma A, Kumar N, Kuppermann BD, et al. Understanding biosimilars and its regulatory aspects across the globe: an ophthalmology perspective. Br J Ophthalmol. 2020;104:2-7. DOI:10.1136/bjophthalmol-2019-314443
  • 3 Warren JB. Generics, chemisimilars and biosimilars: is clinical testing fit for purpose? Br J Clin Pharmacol. 2013;75:7-14. DOI:10.1111/j.1365-2125.2012.04323.x
  • 4 Weise M, Kurki P, Wolff-Holz E, et al. Biosimilars: the science of extrapolation. Blood. 2014;124:3191-6. DOI:10.1182/blood-2014-06-583617
  • 5 Ferrara N and Adamis AP. Ten years of anti-vascular endothelial growth factor therapy. Nat Rev Drug Discov. 2016;15:385-403. DOI:10.1038/nrd.2015.17
  • 6 Desai S, Sekimitsu S, Rossin EJ, et al. Trends in Anti-Vascular Endothelial Growth Factor Original Medicare Part B Claims in the United States, 2014-2019. Ophthalmic Epidemiol. 2024:1-10. DOI:10.1080/09286586.2024.2310854
  • 7 Bressler NM, Kaiser PK, Do DV, et al. Biosimilars of anti-vascular endothelial growth factor for ophthalmic diseases: A review. Surv Ophthalmol. 2024;69:521-38. DOI:10.1016/j.survophthal.2024.03.009
  • 8 Sharma A, Kumar N, Kuppermann BD, et al. Ophthalmic biosimilars: Lessons from India. Indian J Ophthalmol. 2019;67:1384-5. DOI:10.4103/ijo.IJO_430_19
  • 9 Sharma A, Kondo M, Iwahashi C, et al. Approved biosimilar ranibizumab-a global update. Eye (Lond). 2023;37:200-2. DOI:10.1038/s41433-022-02246-5
  • 10 Woo SJ, Veith M, Hamouz J, et al. 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. JAMA Ophthalmol. 2021;139:68-76. DOI:10.1001/jamaophthalmol.2020.5053
  • 11 Anonymous. A Multi Center, Randomized, Double-Masked, Active-Controlled, Comparative Clinical Study to Evaluate the Efficacy and Safety of MYL-1701P and Eylea® in Subjects With Diabetic Macular Edema (DME). In: Momenta Pharmaceuticals I, ed.; 2018.
  • 12 Anonymous. Academy Board of Trustees. Policy Statement. The use of biosimilars in ophthalmic practice. American Academy of Ophthalmology. 2022. Accessed on: June 18. https://www.aao.org/education/clinical-statement/use-of-biosimilars-in-ophthalmic-practice
  • 13 Warudkar S. Retrospective efficacy and safety analysis of zybev (biosimilar of bevacizumab) use at tertiary eye care centres in India: Spectra study. Int J Adv Res. 2018;6:406-10.
  • 14 Agarwal R, Gupta SK and Agrawal S. Efficacy and safety analysis of intravitreal bio-similar products of bevacizumab in patients with macular edema because of retinal diseases. Indian J Ophthalmol. 2023;71:2066-70. DOI:10.4103/ijo.IJO_1748_22
  • 15 Lashay A, Faghihi H, Mirshahi A, et al. Safety of Intravitreal Injection of Stivant, a Biosimilar to Bevacizumab, in Rabbit Eyes. J Ophthalmic Vis Res. 2020;15:341-50. DOI:10.18502/jovr.v15i3.7453
  • 16 Mirshahi A, Lashay A, Riazi-Esfahani H, et al. Intraocular Injection of StivantⓇ (A Biosimilar to Bevacizumab): A Case Series. J Ophthalmic Vis Res. 2021;16:28-33. DOI:10.18502/jovr.v16i1.8248
  • 17 Peraza MA, Hurst S, Huang W, et al. Ocular Safety and Toxicokinetics of Bevacizumab-bvzr (Zirabev), a Bevacizumab Biosimilar, Administered to Cynomolgus Monkeys by Intravitreal Injection. J Ocul Pharmacol Ther. 2023;39:215-24. DOI:10.1089/jop.2022.0059
  • 18 Jung EE, Lee TC and Nagiel A. Initial Experience With Biosimilar Bevacizumab-bvzr For Intravitreal Use in Children: A Case Series and Literature Review. Ophthalmic Surg Lasers Imaging Retina. 2023;54:84-8. DOI:10.3928/23258160-20230130-01
  • 19 Chakraborty S and Sheth JU. Efficacy of an Indian Bevacizumab BIOSimilar (BEVATAS) for Type 1 and Aggressive Posterior Retinopathy of Prematurity (BIOS-ROP Study). Clin Ophthalmol. 2024;18:61-8. DOI:10.2147/opth.S443104
  • 20 Lombardo M, Missiroli F, Cerri L, et al. Real-World Use of Off-Label MVASI in the Treatment of Patients With Neovascular AMD and DME. Transl Vis Sci Technol. 2024;13:17. DOI:10.1167/tvst.13.7.17
  • 21 Casak SJ, Lemery SJ, Chung J, et al. FDA's Approval of the First Biosimilar to Bevacizumab. Clin Cancer Res. 2018;24:4365-70. DOI:10.1158/1078-0432.Ccr-18-0566
  • 22 Anonymous. Birinci Mükerrer Resmi Gazete. Sosyal Güvenlik Kurumu Sağlık Uygulama Tebliğinde Değişiklik Yapılmasına Dair Tebliğ. Accessed on: July 18th. https://www.resmigazete.gov.tr/eskiler/2018/12/20181228M1.htm
  • 23 Karabaş VL, Önder Tokuç E and Şermet F. Survey of Intravitreal Injection Preferences for the Treatment of Age-Related Macular Degeneration and Macular Edema Among Members of the Turkish Ophthalmological Association. Turk J Ophthalmol. 2022;52:179-85. DOI:10.4274/tjo.galenos.2021.37075
  • 24 Biçer AE and Özçelikay AT. Hastanelerde İlaç Tedarik Zinciri ve Devlet Malzeme Ofisi. Eurasian Journal of Health Technology Assessment. 2023;7:120-33. DOI:10.52148/ehta.1409860
  • 25 Schulze-Bonsel K, Feltgen N, Burau H, et al. Visual acuities "hand motion" and "counting fingers" can be quantified with the freiburg visual acuity test. Invest Ophthalmol Vis Sci. 2006;47:1236-40. DOI:10.1167/iovs.05-0981
  • 26 Scartozzi R, Chao JR, Walsh AC, Eliott D. Bilateral improvement of persistent diffuse diabetic macular oedema after unilateral intravitreal bevacizumab (Avastin) injection. Eye (Lond). 2009;5:1229. DOI: 10.1038/eye.2008.162

Real-Life Comparison of Off-Label Intravitreal Biosimilar Bevacizumab-awwb and Reference Bevacizumab in Treatment-Naïve Patients with Neovascular Age-Related Macular Degeneration, Diabetic Macular Edema, and Retinal Vein Occlusion

Year 2025, Volume: 16 Issue: 3, 352 - 361, 01.07.2025

Mehmet Orkun Sevik , Simge Gizem Koyu , Aslan Aykut , Didem Dizdar Yiğit , Özlem Şahin

https://doi.org/10.31067/acusaglik.1528212

Abstract

Purpose: To compare the functional, anatomical, and safety results of intravitreal biosimilar bevacizumab-awwb (IVB-awwb; Mvasi®) and reference bevacizumab (IVB; Altuzan®) in patients with neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and macular edema secondary to retinal vein occlusion (RVO).
Methods: This non-randomized, retrospective, real-life study included 191 treatment-naïve eyes (62 nAMD, 96 DME, and 33 RVO) of 150 patients receiving three monthly IVB and IVB-awwb loading doses. Baseline and final (one month after the third injection) best-corrected visual acuity (BCVA; logMAR) and central macular thickness (CMT; µm) of the eyes with nAMD, DME, and RVO, disease activity rates for nAMD, and overall endophthalmitis rates were compared between IVB and IVB-awwb groups.
Results: The mean baseline and final BCVA and CMT were comparable for nAMD (32 vs. 30 eyes), DME (47 vs. 49 eyes), and RVO (14 vs. 19 eyes) in IVB and IVB-awwb groups. The final nAMD activity rates were 53.1% and 63.3% in the groups, respectively (p=0.578). In DME eyes, BCVA significantly improved in the IVB group (p=0.002) with no significant difference in the IVB-awwb group (p=0.152), and the mean change in BCVA was -0.180.38 and -0.090.45 logMAR, respectively (p=0.033). Culture-negative endophthalmitis (n=2; 2.0% overall) was observed only in the IVB-awwb group (p=0.498).
Conclusion: This real-life study suggests that intravitreal biosimilar bevacizumab-awwb could yield comparable or worse but no better results than reference bevacizumab in eyes with nAMD, DME, and macular edema secondary to RVO. Further randomized studies are required to elucidate the efficacy and safety of IVB-awwb.

Keywords

bevacizumab biosimilar pharmaceuticals diabetic retinopathy macular degeneration macular edema retinal vein occlusion

Ethical Statement

The study protocol was approved by the institutional review board of Marmara University School of Medicine, Istanbul, Turkey (No: 09.2023.873, 09.2023.874, and 09.2023.875).

Supporting Institution

Not applicable.

Project Number

Not applicable.

Thanks

Not applicable.

References

  • 1 Constable I, Shen WY and Rakoczy E. Emerging biological therapies for age-related macula degeneration. Expert Opin Biol Ther. 2005;5:1373-85. DOI:10.1517/14712598.5.10.1373
  • 2 Sharma A, Kumar N, Kuppermann BD, et al. Understanding biosimilars and its regulatory aspects across the globe: an ophthalmology perspective. Br J Ophthalmol. 2020;104:2-7. DOI:10.1136/bjophthalmol-2019-314443
  • 3 Warren JB. Generics, chemisimilars and biosimilars: is clinical testing fit for purpose? Br J Clin Pharmacol. 2013;75:7-14. DOI:10.1111/j.1365-2125.2012.04323.x
  • 4 Weise M, Kurki P, Wolff-Holz E, et al. Biosimilars: the science of extrapolation. Blood. 2014;124:3191-6. DOI:10.1182/blood-2014-06-583617
  • 5 Ferrara N and Adamis AP. Ten years of anti-vascular endothelial growth factor therapy. Nat Rev Drug Discov. 2016;15:385-403. DOI:10.1038/nrd.2015.17
  • 6 Desai S, Sekimitsu S, Rossin EJ, et al. Trends in Anti-Vascular Endothelial Growth Factor Original Medicare Part B Claims in the United States, 2014-2019. Ophthalmic Epidemiol. 2024:1-10. DOI:10.1080/09286586.2024.2310854
  • 7 Bressler NM, Kaiser PK, Do DV, et al. Biosimilars of anti-vascular endothelial growth factor for ophthalmic diseases: A review. Surv Ophthalmol. 2024;69:521-38. DOI:10.1016/j.survophthal.2024.03.009
  • 8 Sharma A, Kumar N, Kuppermann BD, et al. Ophthalmic biosimilars: Lessons from India. Indian J Ophthalmol. 2019;67:1384-5. DOI:10.4103/ijo.IJO_430_19
  • 9 Sharma A, Kondo M, Iwahashi C, et al. Approved biosimilar ranibizumab-a global update. Eye (Lond). 2023;37:200-2. DOI:10.1038/s41433-022-02246-5
  • 10 Woo SJ, Veith M, Hamouz J, et al. 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. JAMA Ophthalmol. 2021;139:68-76. DOI:10.1001/jamaophthalmol.2020.5053
  • 11 Anonymous. A Multi Center, Randomized, Double-Masked, Active-Controlled, Comparative Clinical Study to Evaluate the Efficacy and Safety of MYL-1701P and Eylea® in Subjects With Diabetic Macular Edema (DME). In: Momenta Pharmaceuticals I, ed.; 2018.
  • 12 Anonymous. Academy Board of Trustees. Policy Statement. The use of biosimilars in ophthalmic practice. American Academy of Ophthalmology. 2022. Accessed on: June 18. https://www.aao.org/education/clinical-statement/use-of-biosimilars-in-ophthalmic-practice
  • 13 Warudkar S. Retrospective efficacy and safety analysis of zybev (biosimilar of bevacizumab) use at tertiary eye care centres in India: Spectra study. Int J Adv Res. 2018;6:406-10.
  • 14 Agarwal R, Gupta SK and Agrawal S. Efficacy and safety analysis of intravitreal bio-similar products of bevacizumab in patients with macular edema because of retinal diseases. Indian J Ophthalmol. 2023;71:2066-70. DOI:10.4103/ijo.IJO_1748_22
  • 15 Lashay A, Faghihi H, Mirshahi A, et al. Safety of Intravitreal Injection of Stivant, a Biosimilar to Bevacizumab, in Rabbit Eyes. J Ophthalmic Vis Res. 2020;15:341-50. DOI:10.18502/jovr.v15i3.7453
  • 16 Mirshahi A, Lashay A, Riazi-Esfahani H, et al. Intraocular Injection of StivantⓇ (A Biosimilar to Bevacizumab): A Case Series. J Ophthalmic Vis Res. 2021;16:28-33. DOI:10.18502/jovr.v16i1.8248
  • 17 Peraza MA, Hurst S, Huang W, et al. Ocular Safety and Toxicokinetics of Bevacizumab-bvzr (Zirabev), a Bevacizumab Biosimilar, Administered to Cynomolgus Monkeys by Intravitreal Injection. J Ocul Pharmacol Ther. 2023;39:215-24. DOI:10.1089/jop.2022.0059
  • 18 Jung EE, Lee TC and Nagiel A. Initial Experience With Biosimilar Bevacizumab-bvzr For Intravitreal Use in Children: A Case Series and Literature Review. Ophthalmic Surg Lasers Imaging Retina. 2023;54:84-8. DOI:10.3928/23258160-20230130-01
  • 19 Chakraborty S and Sheth JU. Efficacy of an Indian Bevacizumab BIOSimilar (BEVATAS) for Type 1 and Aggressive Posterior Retinopathy of Prematurity (BIOS-ROP Study). Clin Ophthalmol. 2024;18:61-8. DOI:10.2147/opth.S443104
  • 20 Lombardo M, Missiroli F, Cerri L, et al. Real-World Use of Off-Label MVASI in the Treatment of Patients With Neovascular AMD and DME. Transl Vis Sci Technol. 2024;13:17. DOI:10.1167/tvst.13.7.17
  • 21 Casak SJ, Lemery SJ, Chung J, et al. FDA's Approval of the First Biosimilar to Bevacizumab. Clin Cancer Res. 2018;24:4365-70. DOI:10.1158/1078-0432.Ccr-18-0566
  • 22 Anonymous. Birinci Mükerrer Resmi Gazete. Sosyal Güvenlik Kurumu Sağlık Uygulama Tebliğinde Değişiklik Yapılmasına Dair Tebliğ. Accessed on: July 18th. https://www.resmigazete.gov.tr/eskiler/2018/12/20181228M1.htm
  • 23 Karabaş VL, Önder Tokuç E and Şermet F. Survey of Intravitreal Injection Preferences for the Treatment of Age-Related Macular Degeneration and Macular Edema Among Members of the Turkish Ophthalmological Association. Turk J Ophthalmol. 2022;52:179-85. DOI:10.4274/tjo.galenos.2021.37075
  • 24 Biçer AE and Özçelikay AT. Hastanelerde İlaç Tedarik Zinciri ve Devlet Malzeme Ofisi. Eurasian Journal of Health Technology Assessment. 2023;7:120-33. DOI:10.52148/ehta.1409860
  • 25 Schulze-Bonsel K, Feltgen N, Burau H, et al. Visual acuities "hand motion" and "counting fingers" can be quantified with the freiburg visual acuity test. Invest Ophthalmol Vis Sci. 2006;47:1236-40. DOI:10.1167/iovs.05-0981
  • 26 Scartozzi R, Chao JR, Walsh AC, Eliott D. Bilateral improvement of persistent diffuse diabetic macular oedema after unilateral intravitreal bevacizumab (Avastin) injection. Eye (Lond). 2009;5:1229. DOI: 10.1038/eye.2008.162
There are 26 citations in total.

Details

Primary Language English
Subjects Ophthalmology
Journal Section Research Articles
Authors

Mehmet Orkun Sevik 0000-0001-7130-4798

Simge Gizem Koyu 0000-0003-2035-1273

Aslan Aykut 0000-0001-5426-1992

Didem Dizdar Yiğit 0000-0001-7309-3293

Özlem Şahin 0000-0003-2907-2852

Project Number Not applicable.
Publication Date July 1, 2025
Submission Date August 5, 2024
Acceptance Date January 29, 2025
Published in Issue Year 2025Volume: 16 Issue: 3

Cite

EndNote Sevik MO, Koyu SG, Aykut A, Dizdar Yiğit D, Şahin Ö (July 1, 2025) Real-Life Comparison of Off-Label Intravitreal Biosimilar Bevacizumab-awwb and Reference Bevacizumab in Treatment-Naïve Patients with Neovascular Age-Related Macular Degeneration, Diabetic Macular Edema, and Retinal Vein Occlusion. Acıbadem Üniversitesi Sağlık Bilimleri Dergisi 16 3 352–361.
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