Why is there no biosimilar of Erbitux®?

Douez, Emmanuel; D’Atri, Valentina; Guillarme, Davy; Antier, Daniel; Guerriaud, Mathieu; Beck, Alain; Watier, Hervé; Foucault-Fruchard, Laura

doi:10.1016/j.jpba.2023.115544

Cited by 8 publications

(4 citation statements)

References 54 publications

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“…It successfully profiled the glycans of various IgG mAbs, including IgG1, IgG2, IgG4, ADC, and Fc-fusion proteins. Our findings aligned with previous reports, highlighting core fucose on predominant G0F and G1F glycans in NISTmAb ( Figures 2c and 3a ), 34 terminal GlcNAc on the main G0 glycan in benralizumab ( Figure 3b ), 35 terminal β-galactose, high mannose, α2,6-linked sialic acid, and α-galactose in cetuximab ( Figures 2a, 2b ), 23 , 25 , 26 and elevated levels of tri/tetra-antennary and α2,3-linked sialic acids in CHO-produced protein darbepoetin alfa ( Figure 2c ). 27 , 28 Additionally, our nine-lectin microarray exhibited remarkable sensitivity to terminal glycan alterations, exemplified by targeted glycoengineering of IgG1 mAbs, encompassing galactosylation, α2,3-sialylation, and removal of terminal monosaccharide such as GlcNAc, high mannose, bisecting GlcNAc, α-galactose, and α2,6-sialic acids ( Figure 3 ).…”

Section: Discussionsupporting

confidence: 93%

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A tailored lectin microarray for rapid glycan profiling of therapeutic monoclonal antibodies

Luo,

Zhang

2024

mAbs

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Glycosylation plays a crucial role in determining the quality and efficacy of therapeutic antibodies. This necessitates a thorough analysis and monitoring process to ensure consistent product quality during manufacturing. In this study, we introduce a custom-designed lectin microarray featuring nine distinct lectins: rPhoSL, rOTH3, RCA120, rMan2, MAL_I, rPSL1a, PHAE, rMOA, and PHAL. These lectins have been specifically tailored to selectively bind to common N-glycan epitopes found in therapeutic IgG antibodies. By utilizing intact glycoprotein samples, our nine-lectin microarray provides a high-throughput platform for rapid glycan profiling, enabling comparative analysis of glycosylation patterns. Our results demonstrate the practical utility of this microarray in assessing glycosylation across various manufacturing batches or between biosimilar and innovator products. This capacity empowers informed decision-making in the development and production of therapeutic antibodies.

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Section: Discussionsupporting

confidence: 93%

“…Cetuximab, which is known to possess two N-glycosylation sites on Fc and Fab regions of the IgG1 mAb, 23 , 25 displayed distinct lectin-binding patterns. Specifically, it exhibited binding to rPSL1a and rMOA (as depicted in Figure 2a,b ).…”

Section: Resultsmentioning

confidence: 99%

A tailored lectin microarray for rapid glycan profiling of therapeutic monoclonal antibodies

Luo,

Zhang

2024

mAbs

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“…In addition to TKIs, there are monoclonal antibodies such as cetuximab and panitumumab that target and inactivate EGFR receptors. Cetuximab is an IgG monoclonal antibody against EGFRvIII and wildtype EGFR that has been successful in the treatment of metastatic colorectal cancer and squamous head and neck cancer (Figure 1) [43,44]. Panitumumab is a monoclonal antibody antagonist of wildtype EGFR that has found success in the treatment of colorectal carcinoma [45].…”

Section: Egfr Inhibitors In Glioblastoma: Preclinical Studiesmentioning

confidence: 99%

Epidermal Growth Factor Receptor Inhibitors in Glioblastoma: Current Status and Future Possibilities

Ezzati,

Salib,

Balasubramaniam

et al. 2024

IJMS

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Glioblastoma, a grade 4 glioma as per the World Health Organization, poses a challenge in adult primary brain tumor management despite advanced surgical techniques and multimodal therapies. This review delves into the potential of targeting epidermal growth factor receptor (EGFR) with small-molecule inhibitors and antibodies as a treatment strategy. EGFR, a mutationally active receptor tyrosine kinase in over 50% of glioblastoma cases, features variants like EGFRvIII, EGFRvII and missense mutations, necessitating a deep understanding of their structures and signaling pathways. Although EGFR inhibitors have demonstrated efficacy in other cancers, their application in glioblastoma is hindered by blood–brain barrier penetration and intrinsic resistance. The evolving realm of nanodrugs and convection-enhanced delivery offers promise in ensuring precise drug delivery to the brain. Critical to success is the identification of glioblastoma patient populations that benefit from EGFR inhibitors. Tools like radiolabeled anti-EGFR antibody 806i facilitate the visualization of EGFR conformations, aiding in tailored treatment selection. Recognizing the synergistic potential of combination therapies with downstream targets like mTOR, PI3k, and HDACs is pivotal for enhancing EGFR inhibitor efficacy. In conclusion, the era of precision oncology holds promise for targeting EGFR in glioblastoma, contingent on tailored treatments, effective blood–brain barrier navigation, and the exploration of synergistic therapies.

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“…However, recent studies have shown that KRAS mutations are detected in 36–46% of colorectal cancer cases, rendering cetuximab ineffective for the treatment of such patients [ 9 , 10 , 11 ]. Despite the expiration of the patent in Europe in 2014 and projected annual sales of approximately USD 1.681 million in 2022, Erbitux ® has not yet faced any approved biosimilar challenges in the United States or in Europe [ 12 ]. The exorbitant costs associated with multiple treatment courses underscore the pressing need for novel anti-EGFR agents.…”

Section: Introductionmentioning

confidence: 99%

Preclinical Pharmacokinetics and Biodistribution of LR004, a Novel Antiepidermal Growth Factor Receptor Monoclonal Antibody

Zheng,

Dou,

Liu

et al. 2024

Molecules

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LR004 is a novel chimeric (human/mouse) monoclonal antibody developed for the treatment of advanced colorectal carcinoma with detectable epidermal growth factor receptor (EGFR) expression. We aimed to investigate the preclinical pharmacokinetics (PK) and in vivo biodistribution of LR004. The PK profiles of LR004 were initially established in rhesus monkeys. Subsequently, 125I radionuclide-labeled LR004 was developed and the biodistribution, autoradiography, and NanoSPECT/CT of 125I-LR004 in xenograft mice bearing A431 tumors were examined. The PK data revealed a prolonged half-life and nonlinear PK characteristics of LR004 within the dose range of 6–54 mg/kg. The radiochemical purity of 125I-LR004 was approximately 98.54%, and iodination of LR004 did not affect its specific binding activity to the EGFR antigen. In a classical biodistribution study, 125I-LR004 exhibited higher uptake in highly perfused organs than in poorly perfused organs. Prolonged retention properties of 125I-LR004 in tumors were observed at 4 and 10 days. Autoradiography and NanoSPECT/CT confirmed the sustained retention of 125I-LR004 at the tumor site in xenograft mice. These findings demonstrated the adequate tumor targeting capabilities of 125I-LR004 in EGFR-positive tumors, which may improve dosing strategies and future drug development.

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Why is there no biosimilar of Erbitux®?

Cited by 8 publications

References 54 publications

A tailored lectin microarray for rapid glycan profiling of therapeutic monoclonal antibodies

A tailored lectin microarray for rapid glycan profiling of therapeutic monoclonal antibodies

Epidermal Growth Factor Receptor Inhibitors in Glioblastoma: Current Status and Future Possibilities

Preclinical Pharmacokinetics and Biodistribution of LR004, a Novel Antiepidermal Growth Factor Receptor Monoclonal Antibody

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