Investigation of Factors Associated With Immunogenicity Labeling Updates and Characteristics of Biologics License Applications

Jiang, Ai Lei; Breder, Christopher D.; Chang, Lin-Chau

doi:10.1002/cpt.2393

Cited by 1 publication

(6 citation statements)

References 26 publications

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“…1,13,25 These findings highlighted the unpredictability and complexity of immunogenicity evaluation. 24,26 The remaining uncertainty of immunogenicity concerns in the reference biologics makes the development of biosimilars more challenging. 12,27,28 Therefore, both the European Medicines Agency (EMA) and the FDA have published guidelines for biosimilars providing recommendations for immunogenicity assessment.…”

Section: Investigation Of Immunogenicity Assessment Of Biosimilar Mon...mentioning

confidence: 99%

“…Uncertainties remained in the labeling documents of reference biologics awaiting PMRs for more evidence. 26 In terms of PK and efficacy, most of the original labeling documents of reference products did not mention the impact of ADAs. 26,46,47 The uncertainties made the interpretation of the findings of biosimilars more challenging.…”

Section: Challenges In Immunogenicity Assessmentmentioning

confidence: 99%

“…26 In terms of PK and efficacy, most of the original labeling documents of reference products did not mention the impact of ADAs. 26,46,47 The uncertainties made the interpretation of the findings of biosimilars more challenging. Often, it was less likely to reach statistically significant differences for ADA/NAb impact in the trials conducted for biosimilar applications due to small sample sizes.…”

Section: Challenges In Immunogenicity Assessmentmentioning

confidence: 99%

“…However, the information provided in the labeling of reference products about the impact of ADA and NAb might not be comprehensive enough, leading to uncertainties about their implications and long-term effects. 1,26,42 Our research, based on the analysis of approved biosimilar applications, has shed light on the importance of revisiting immunogenicity assessment and the challenges of obtaining sufficient evidence before approval. Regulatory considerations for immunogenicity studies prioritize assessing the impact on clinical consequences over differences in ADA incidence.…”

Section: Challenges In Immunogenicity Assessmentmentioning

confidence: 99%

“…However, studies implied that there was a lack of sufficient critical information, such as the clinical significance of being ADA‐ or NAb‐positive, or the long‐term immunogenicity, in many reference biologics labeling documents and an over‐reliance on further post‐marketing evidence 1,13,25 . These findings highlighted the unpredictability and complexity of immunogenicity evaluation 24,26 …”

mentioning

confidence: 99%

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Investigation of Immunogenicity Assessment of Biosimilar Monoclonal Antibodies in the United States

Cheng,

Jiang,

Liu

et al. 2023

Clin Pharma and Therapeutics

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Immunogenicity is critical for biologics. However, reference biologics labeling documents do not necessarily mention immunogenicity impact, rendering the development of biosimilars more challenging. We aimed to investigate the comparative assessment of immunogenicity profiles between biosimilars and their respective reference biologics in the review reports of the biosimilar monoclonal antibody applications approved by the Center for Drug Evaluation and Research (CDER), US Food and Drug Administration (FDA) as of March 13, 2022, covering 22 applications approved between April 5, 2016, and December 17, 2021. The maximum differences in anti‐drug antibody (ADA) and neutralizing antibody (NAb) incidences between biosimilars and reference products mostly fell within ± 15% (−13.6% to 12%) and ± 20% (−17.4% to 17.1%, except extreme values of −23.4% and 66.7%), respectively. In comparison with antineoplastic agents, more immunosuppressants had ADA‐positive (11/11, 100.0% vs. 8/10, 80.0%)/NAb‐positive (11/11, 100.0% vs. 3/10, 30.0%) subjects, and the distribution of the aforementioned incidence differences was wider. The investigated biosimilars with available data for analysis demonstrated a high degree of consistency with their reference products in terms of the impact on pharmacokinetic parameters. No increase in immunogenicity was found in available switching studies. Most (16/22, 72.7%) biosimilars were issued post‐marketing requirements that were not directly related to immunogenicity concerns. The FDA considered the totality of evidence assessing clinical consequences of immunogenicity differences, if any. Additional information on titers and subgroup analysis may be warranted to elucidate the critical attributes of immunogenicity impact and to aid in forming cost‐effective strategies for biosimilar development.

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