An article entitled “Investigation of Immunogenicity Assessment of Biosimilar Monoclonal Antibodies in the United States” by Ching-An Cheng, Ai-Lei Jiang, Yu-Ru Liu and Lin-Chau Chang, is published in the journal, Clinical Pharmacology & Therapeutics, on 27 August 2023. This article investigated 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. The study found that the maximum differences in anti-drug antibody (ADA) and neutralizing antibody (NAb) incidences between biosimilars and reference products mostly fell within ±15% (-13.6%~12%) and ±20% (-17.4%~17.1%, except extreme values of -23.4% and 66.7%), respectively. In comparison with antineoplastic agents, more immunosuppressants had ADA- (11/11, 100.0% versus 8/10, 80.0%)/NAb- (11/11, 100.0% versus 3/10, 30.0%) positive 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 the 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 USFDA 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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感謝「臺大藥學發展永續基金計畫」對於國際藥政法規科學研究平台之支持，鄭慶安、姜愛蕾、劉育汝、張琳巧，以“Investigation of Immunogenicity Assessment of Biosimilar Monoclonal Antibodies in the United States”為題之文章，已於2023年8月27日發表於Clinical Pharmacology & Therapeutics期刊。此研究調查截至2022年3月13日為止，美國食品藥物管理局 (FDA) 藥物評估與研究中心 (CDER) 批准的單株抗體生物相似藥 (biosimilar) 申請案審核報告中，生物相似藥與其對照生物製劑的免疫原性特徵之比較評估。研究結果顯示，生物相似藥與對照生物製劑之間的抗藥抗體 (ADA) 和中和抗體 (NAb) 發生率的最大差異，大部分落在±15% (-13.6%〜12%) 和±20% (-17.4%〜17.1%，除了-23.4%和66.7%的極端值) 之間。與抗腫瘤藥物相比，更多的免疫抑制劑具有ADA陽性 (11/11，100.0%對比8/10，80.0%)/NAb陽性 (11/11，100.0%對比3/10，30.0%) 受試者，且發生率差異的分布範圍更廣。含可供分析數據之的生物相似藥申請案，在藥物動力學參數影響方面與其對照生物製劑具高度一致性。於現有的換藥研究中，並未發現免疫原性的增加。大多數 (16/22，72.7%) 生物相似藥申請案之上市後要求與免疫原性議題不直接相關。假使免疫原性結果顯示其可能具差異性，美國FDA以證據整體是否呈現對於臨床反應具顯著影響進行評估。若能額外進行抗體效價和次群體分析，將可能有助於闡明免疫原性影響的關鍵屬性，並有助於制定具成本效益之開發生物相似藥的策略。
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