Ranibizumab Biosimilars in Treating Retinal Disorders: A Cost-Effective Revolution?

Figures & data

Table 1 Overview of Studies on the Use of Ranibizumab Biosimilars in nAMD

Author Year	Biosimilar	Number of Eyes	Key Findings
Sharma et al 2020^Citation10	Razumab^® Intas Pharmaceuticals, India	103	The average BCVA and subfield thickness was significantly improved at all time endpoints. IOP changed minimally and not significantly. Decrease in proportions of patients having IRF or SRF.
Holz et al 2021^Citation3	FYB201 (bioeq GmbH, Holzkirchen, Germany)	477	BCVA improved +5.1 (in the FYB201 group) and +5.6 ETDRS letters in the reference ranibizumab group at week 8. Primary endpoint was met as the 90% CI was within the predefined equivalence margin. Adverse events were comparable between treatment groups.
Woo et al 2023^Citation5	SB11 (Samsung Bioepis)	705	Mean BCVA changed from baseline at week 8 6.2 (0.5) letters in the SB11 group and 7.0 (0.5) letters in the ranibizumab group. Changes of SE in CST from baseline at week 4 were −108 (5) μm in the SB11 group and −100 (5) μm in the ranibizumab group. Similar occurrence of adverse effects in the SB11 and ranibizumab groups. Low immunogenicity.
Apsangikar et al 2021^Citation24	RanizuRel (Reliance Life Sciences, Mumbai, India)	160	105 patients in the test arm (RanizuRel) lost fewer than 15 letters in BCVA from baseline, compared to 53 patients in the reference arm (ranibizumab). The mean number of letters ETDRS that were gained at 6 months was 15.66 in the group of ranibizumab and 12.11 ETDRS letters in the group of RanizuRel, with a non-significant difference between the two groups (p=0.07534). The mean change in CMT at 6 months was −64.42 µm in the ranibizumab group and −89.93 µm in the biosimilar group without significant difference between the two groups.
Yoon et al 2022^Citation25	CKD-701 (Chong Kun Dang, South Korea)	143	The BCVA improved with a mean improvement of +7.0 (CKD-701) and +6.2 (ranibizumab) letters at 3 months (P = 0.43). The percentage of patients with subretinal or intraretinal fluid at 3, 6, and 12 months did not differ significantly between the groups of the study. The number (SE) of injections was 8.36 (3.13) in the CKD-701 group and 8.26 (2.92) in the reference ranibizumab group (P = 0.62). The incidence of adverse events and immunogenicity were not statistically different in the study arms.
Singh et al 2022^Citation27	Lupin’s Ranibizumab	174	On the 90th day, the calculated treatment contrast between Lupin’s ranibizumab and the innovator ranibizumab group fell within the pre-established equivalence margin of 8.5% concerning the percentage of patients who exhibited a reduction of fewer than 15 letters. Consistent improvement of mean BCVA was reported at days 31, 61, and 90 as compared to the baseline, in both therapeutic groups.
Loewenstein et al 2023^Citation26	XSB-001 (Ximluci; STADA Arzneimittel AG)	582	At week 8, the LS mean (standard error [SE]) change in BCVA from baseline was 4.6 (0.5) ETDRS letters in the XSB-001 group and 6.4 (0.5) letters in the reference ranibizumab group. The 90% CI and 95% CI for LS mean difference in change from baseline were within the predefined equivalence margin. LS mean (SE) change in BCVA was 6.4 (0.8) and 7.8 (0.8) letters, respectively, at week 52. No meaningful differences between treatment groups in anatomical, safety, or immunogenicity end points through week 52.
Chakraborty et al 2023^Citation23	Razumab^® (Intas Pharmaceuticals, India)	164	BCVA was significantly improved from 0.57±0.27 logMAR to 0.41±0.23 at 12 months in the ranibizumab group and from 0.61±0.25 to 0.24±0.16 in the razumab group. CMT was significantly decreased in the razumab group from 407.82±53.07μm at the baseline to 283.09±19.66 μm at week 12. Similar improvement of SRF and IRF without significance. No major adverse effects were noticed.

Abbreviations: BCVA, Best Corrected Visual Acuity; CI, Confidence Interval; CST, Central Subfield Thickness; CMT, Central Macular Thickness; LS, Least Squares, IOP, Intraocular Pressure: SRF, Subretinal Fluid; IRF, Intraretinal Fluid.

Table 2 Overview of Studies on the Use of Ranibizumab Biosimilars in Other Retinal Conditions

Author Year	Biosimilar Tested	Number of Eyes	Disease	Key Findings
Sharma et al 2019^Citation22	Razumab^® Intas Pharmaceuticals, India	160	RVO	Significant BCVA improvement from week 8 (0.55 ± 0.02; p < 0.0001) and week 12 (0.47 ± 0.02; p < 0.0001). Significant decrease in CMT at week 4, 8 and 12. The proportion of patients with IRF and SRF significantly decreased from baseline to weeks 4, 8, and 12.
Prajapati et al 2023^Citation28	Razumab^® Intas Pharmaceuticals, India	118	ROP	Complete resolution of ROP along with complete vascularization was seen in 22 eyes (19%) at a median of 55 days, 42 eyes (35%) showed a recurrent neovascularization at a median of 51 days post injection. The cumulative incidence of recurrence of neovascularization was significantly superior in eyes with APROP (43%, 95% CI = 27%–63%) compared to eyes without APROP (13.4%, 95% CI, 8%-22%) (P < 0.001).
Chakraborty et al 2022^Citation29	Razumab^® Intas Pharmaceuticals, India	333	DME	Mean BCVA improved from 0.71 ± 0.42 logMAR to 0.50 ± 0.29 logMAR in the bRBZ group (p < 0.001) at 6 months. There were no differences in BCVA compared to innovator ranibizumab (p > 0.05 for all time points). The CMT reduction was comparable between the two groups. The mean number of injections did not differ significantly between the two groups (3.81 ± 1.2 in iRBZ vs 3.55 ± 1.2 in bRBZ) (p > 0.05).
Soman et al 2022^Citation30	Razumab^® Intas Pharmaceuticals, India	22	PCV	Comparable visual outcomes to the innovator ranibizumab, good safety profile.
Retra et al 2022^Citation31	Razumab^® Intas Pharmaceuticals, India	202	AMD RVO DME	Comparable results to innovator ranibizumab and bevacizumab. Significant improvement of BCVA at 3 months in the group of AMD and in the group of macular edema due to RVO or DME. CMT was significantly decreased at 3 months in both groups of patients that received the biosimilar razumab. No major complications were reported.

Abbreviations: AMD, Age-related Macular Degeneration; BCVA, Best Corrected Visual Acuity; bRBZ, Biosimilar Ranibizumab; CI, Confidence Interval; CMT, Central Macular Thickness; DME, Diabetic Macular Edema; IOP, Intraocular Pressure; iRBZ, innovator ranibizumab; SRF, Subretinal Fluid; IRF, Intraretinal Fluid; PCV, Polypoidal Choroidal Vasculopathy; ROP, Retinopathy of Prematurity; RVO, Retinal Vein Occlusion.

Sharma S, Khan M, Chaturvedi A; RE-ENACT 2 Study Investigators Group. A Multicenter, Retrospective Study (RE-ENACT 2) on the use of razumabTM (world’s first biosimilar ranibizumab) in wet age-related macular degeneration. Ophthalmol Ther. 2020;9(1):103–114. doi:10.1007/s40123-019-00228-7

 PubMed Web of Science ®Google Scholar

Holz FG, Oleksy P, Ricci F, Kaiser PK, Kiefer J, Schmitz-Valckenberg S. Efficacy and safety of biosimilar FYB201 compared with ranibizumab in neovascular age-related macular degeneration. Ophthalmology. 2022;129(1):54–63. doi:10.1016/j.ophtha.2021.04.031

 PubMed Web of Science ®Google Scholar

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(1):68. doi:10.1001/jamaophthalmol.2020.5053

 PubMed Web of Science ®Google Scholar

Apsangikar P, Ghadge P, Naik M, Nair S, Payghan R. Randomised, double-blind, comparative clinical study of new ranibizumab biosimilar in neovascular (Wet) age-related macular degeneration. Clin Ophthalmol. 2021;15:3087–3095. doi:10.2147/OPTH.S307746

 PubMed Web of Science ®Google Scholar

Yoon CK, Oh J, Bae K, Park UC, Yu KS, Yu HG. Efficacy and safety of a new ranibizumab biosimilar CKD-701 using a pro re nata treatment regimen in neovascular age-related macular degeneration: a phase 3 randomized clinical trial. Vavvas DG, ed. PLoS One. 2022;17(11):e0275611. doi:10.1371/journal.pone.0275611

 PubMed Web of Science ®Google Scholar

Singh R, Chauhan R, Saxena A, et al. A prospective, randomized, parallel group, double blind, multicenter study to compare the efficacy, safety and immunogenicity of lupin’s ranibizumab with lucentis ® in patients with neovascular age-related macular degeneration. Indian J Ophthalmol. 2022;70(8):3008. doi:10.4103/ijo.IJO_2118_21

 PubMed Web of Science ®Google Scholar

Loewenstein A, Czumbel N, Ernest J, Dusová J, Pearlman J, Nowosielska A. Randomized trial of biosimilar XSB-001 versus reference ranibizumab in patients with neovascular age-related macular degeneration. Ophthalmol Retina. 2023;7(9):753–761. doi:10.1016/j.oret.2023.05.005

 PubMedGoogle Scholar

Chakraborty D, Mondal S, Boral S, et al. Biosimilar versus InnovAtor MoLecule of RAnibizumab in neovascular age-related MaCular DEgeneration (The BALANCE Trial): real-world evidence. Clin Ophthalmol. 2023;17:1067–1076. doi:10.2147/OPTH.S407219

 PubMed Web of Science ®Google Scholar

Sharma S, Khan MA, Chaturvedi A; RE-ENACT Study Investigators Group. Real-life clinical effectiveness of razumab® (the world’s first biosimilar of ranibizumab) in retinal vein occlusion: a subgroup analysis of the pooled Retrospective RE-ENACT Study. Ophthalmologica. 2019;241(1):24–31. doi:10.1159/000488602

 PubMed Web of Science ®Google Scholar

Prajapati V, Choudhary T, Chauhan W, et al. Efficacy of a biosimilar ranibizumab monotherapy for the treatment of retinopathy of prematurity. Indian J Ophthalmol. 2023;71(2):411. doi:10.4103/ijo.IJO_973_22

 PubMed Web of Science ®Google Scholar

Chakraborty D, Sengupta S, Mondal S, et al. Comparison of innovator vs. biosimilar ranibizumab in treating diabetic macular edema: a Multicenter Retrospective Study. Ophthalmol Ther. 2022;11(2):629–638. doi:10.1007/s40123-022-00463-5

 PubMed Web of Science ®Google Scholar

Soman M, Nair I, Sheth JU, Nair U. Innovator Versus Biosimilar Ranibizumab in Polypoidal Choroidal Vasculopathy: real-World Evidence. Ophthalmol Ther. 2022;11(3):1175–1186. doi:10.1007/s40123-022-00507-w

 PubMed Web of Science ®Google Scholar

Ratra D, Roy K, Giridhar S, et al. Comparison between ranibizumab biosimilar, innovator ranibizumab and bevacizumab in a real-world situation. Ophthalmol Ther. 2022;11(1):135–149. doi:10.1007/s40123-021-00416-4

 PubMed Web of Science ®Google Scholar