Cost-effectiveness of Aflibercept Monotherapy vs Bevacizumab First Followed by Aflibercept If Needed for Diabetic Macular Edema

Hutton, David; Glassman, Adam R.; Liu, Danni; Sun, Jennifer K.

doi:10.1001/jamaophthalmol.2022.6142

Cited by 8 publications

(2 citation statements)

References 16 publications

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“…This is particularly important since analyses by Data Bridge Market Research suggest that the aflibercept market is expected to undergo a CAGR of 5.4% during a forecast period of 2030 [ 50 ]. It should be noted that the current mammalian cell expression is an expensive process and the resulting high production costs of aflibercept significantly contribute to the enormous price of the final product [ 51 , 52 ].…”

Section: Discussionmentioning

confidence: 99%

Efficient Expression of Functionally Active Aflibercept with Designed N-glycans

Keshvari,

Melnik,

Sun

et al. 2024

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Aflibercept is a therapeutic recombinant fusion protein comprising extracellular domains of human vascular endothelial growth factor receptors (VEGFRs) and IgG1-Fc. It is a highly glycosylated protein with five N-glycosylation sites that might impact it structurally and/or functionally. Aflibercept is produced in mammalian cells and exhibits large glycan heterogeneity, which hampers glycan-associated investigations. Here, we report the expression of aflibercept in a plant-based system with targeted N-glycosylation profiles. Nicotiana benthamiana-based glycoengineering resulted in the production of aflibercept variants carrying designed carbohydrates, namely, N-glycans with terminal GlcNAc and sialic acid residues, herein referred to as AFLIGnGn and AFLISia, respectively. Both variants were transiently expressed in unusually high amounts (2 g/kg fresh leaf material) in leaves and properly assembled to dimers. Mass spectrometric site-specific glycosylation analyses of purified aflibercept showed the presence of two to four glycoforms in a consistent manner. We also demonstrate incomplete occupancy of some glycosites. Both AFLIGnGn and AFLISia displayed similar binding potency to VEGF165, with a tendency of lower binding to variants with increased sialylation. Collectively, we show the expression of functionally active aflibercept in significant amounts with controlled glycosylation. The results provide the basis for further studies in order to generate optimized products in the best-case scenario.

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Section: Discussionmentioning

confidence: 99%

Efficient Expression of Functionally Active Aflibercept with Designed N-glycans

Keshvari,

Melnik,

Sun

et al. 2024

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“…Diabetic macular edema (DME) is a common ocular complication in diabetic patients, 1 and it is the first cause of blindness in adults in Europe and United States. 2 The incidence of macular oedema in patients with type 2 diabetes and patients with type 1 diabetes is 14% and 29%, respectively.…”

Section: Introductionmentioning

confidence: 99%

Aflibercept versus ranibizumab for diabetic macular edema: A meta-analysis

Chen

Shi

Zhang

et al. 2023

European Journal of Ophthalmology

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Objective The purpose of this study was to compare the efficacy and safety of aflibercept (AFL) versus ranibizumab (RAN) for the treatment of diabetic macular edema (DME). Methods The PubMed, Embase, Cochrane Library, and CNKI databases were searched up to September 2022 to identify prospective randomized controlled trials (RCTs) comparing AFL with RAN for the treatment of DME. Review Manager 5.3 software was used for data analysis. We used the GRADE system to evaluate the quality of the evidence for each outcome. Results A total of 8 RCTs involving 1067 eyes (939 patients) were included; there were 526 eyes in the AFL group and 541 eyes in the RAN group. Meta-analysis revealed that there was no significant difference between RAN and AFL in the best-corrected visual acuity (BCVA) of DME patients at 6 months (WMD: −0.05, 95% CI = −0.12 to 0.01, moderate quality) and 12 months after injection (WMD: −0.02, 95% CI = −0.07 to 0.03, moderate quality). Additionally, there was no significant difference between RAN and AFL in the reduction of central macular thickness (CMT) at 6 months (WMD: −0.36, 95% CI = −24.99 to 24.26, very low quality) and 12 months after injection (WMD: −6.36, 95% CI = −16.30 to 3.59, low quality). Meta-analysis showed that the number of intravitreal injections (IVIs) for AFL was significantly lower than that for RAN (WMD: −0.47, 95% CI = −0.88 to −0.05, very low quality). There were fewer adverse reactions to AFL than to RAN, but the difference was not significant. Conclusion This study found that there was no difference in BCVA, CMT or adverse reactions between AFL and RAN at 6 and 12 months of follow-up, but AFL needed fewer IVIs than RAN.

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Cost-effectiveness Analysis of Ranibizumab Biosimilar for Neovascular Age-Related Macular Degeneration and its Subtypes from the Societal and Patient Perspectives in Japan

Yanagi,

Takahashi,

Iida

et al. 2024

Ophthalmol Ther

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Introduction This study evaluated the cost-effectiveness of anti-vascular endothelial growth factor (VEGF) therapies for subtypes of neovascular age-related macular degeneration (nAMD) from the societal perspective, and for any nAMD from the patient perspective in Japan. Methods A Markov model was developed to simulate the lifetime transitions of a cohort of patients with nAMD through various health states based on the involvement of nAMD, the treatment status, and decimal best-corrected visual acuity. Ranibizumab biosimilar was compared with aflibercept from the societal perspective regardless of treatment regimen for the analysis of three subtypes (typical nAMD, polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP)). Two analyses from the patient perspective focusing on the treat-and-extend regimens were performed, one with a cap on patients’ copayments and one without. Ranibizumab biosimilar was compared with branded ranibizumab, aflibercept, aflibercept as the loading dose switching to ranibizumab biosimilar during maintenance (aflibercept switching to ranibizumab biosimilar), and best supportive care (BSC), for patients with any nAMD. Results In the subtype analyses, ranibizumab biosimilar when compared with aflibercept resulted in incremental quality-adjusted life years (QALYs) of − 0.015, 0.026, and 0.009, and the incremental costs of Japanese yen (JPY) − 50,447, JPY − 997,243, and JPY − 1,286,570 for typical nAMD, PCV, and RAP, respectively. From the patient perspective, ranibizumab biosimilar had incremental QALYs of 0.015, 0.009, and 0.307, compared with aflibercept, aflibercept switching to ranibizumab biosimilar, and BSC, respectively. The incremental costs for ranibizumab biosimilar over a patient lifetime excluding the cap on copayment were estimated to be JPY − 138,948, JPY − 391,935, JPY − 209,099, and JPY − 6,377,345, compared with branded ranibizumab, aflibercept, aflibercept switching to ranibizumab biosimilar, and BSC, respectively. Conclusions Ranibizumab biosimilar was demonstrated as a cost-saving option compared to aflibercept across all subtypes of nAMD, irrespective of the perspectives considered. Supplementary Information The online version contains supplementary material available at 10.1007/s40123-024-01011-z.

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Cost-effectiveness of Aflibercept Monotherapy vs Bevacizumab First Followed by Aflibercept If Needed for Diabetic Macular Edema

Cited by 8 publications

References 16 publications

Efficient Expression of Functionally Active Aflibercept with Designed N-glycans

Efficient Expression of Functionally Active Aflibercept with Designed N-glycans

Aflibercept versus ranibizumab for diabetic macular edema: A meta-analysis

Cost-effectiveness Analysis of Ranibizumab Biosimilar for Neovascular Age-Related Macular Degeneration and its Subtypes from the Societal and Patient Perspectives in Japan

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