ファセンラ:Benralizumabの攻撃対象題材となるかもしれない
Immunogenicity :antidrug antibody (ADA) assay
Understanding the Supersensitive Anti-Drug Antibody Assay: Unexpected High Anti-Drug Antibody Incidence and Its Clinical Relevance
Journal of Immunology Research Volume 2016 (2016), Article ID 3072586, 8 pages
http://dx.doi.org/10.1155/2016/3072586
最近の免疫原性検査で異常に効率に免疫原性陽性率認めることがあり、完全ヒト型抗体でさえ、検出される。supersensitiveな検査から、ADAが容易に検出されるようになった。
時代背景から、喘息関連のBio製剤でも問題になってきた
Benralizumab
Out of 19 subjects treated with multiple doses of benralizumab, 4 exhibited evidence of immunogenicity (as measured by anti-drug antibodies).
In the 10-mg group, ADAs were detected in 3 subjects on day 8. One of these 3 subjects also tested positive for ADAs on day 29. No ADAs were detected after day 29.Benralizumab – a humanized mAb to IL-5Rα with enhanced antibody-dependent cell-mediated cytotoxicity – a novel approach for the treatment of asthma
One subject in the 75-mg group and 1 subject in the 250-mg group tested positive for ADAs on day 8; both subjects tested negative at the later times. No ADAs were detected in any subjects in the 750-mg or placebo group up to day 151 postdose. None of the samples that tested ADA positive tested positive for neutralizing activity.
Aasia Ghazi, et al.
Expert Opin Biol Ther. Author manuscript; available in PMC 2013 Mar 4.
Overall, treatment-emergent anti-drug antibody response developed in 13% of patients treated with FASENRA at the recommended dosing regimen during the 48 to 56 week treatment period. A total of 12% of patients treated with FASENRA developed neutralizing antibodies. Anti-benralizumab antibodies were associated with increased clearance of benralizumab and increased blood eosinophil levels in patients with high anti-drug antibody titers compared to antibody negative patients. No evidence of an association of anti-drug antibodies with efficacy or safety was observed. The data reflect the percentage of patients whose test results were positive for antibodies to benralizumab in specific assays.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761070s000lbl.pdf
ヌーカラ
Pharmacokinetics and Pharmacodynamics of Mepolizumab, an Anti–Interleukin 5 Monoclonal Antibody, in HealthyJapanese Male Subjects
Naohiro Tsukamoto, et al.
Clinical Pharmacology in Drug Development
Submitted for publication 14 January 2015; accepted 4 June 2015
https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125526Orig1s000Lbl.pdfOverall, 15/260 (6%) of subjects treated with NUCALA developed anti-mepolizumab antibodies. The reported frequency may underestimate the actual frequency due to lower assay sensitivity in the presence of high drug concentration. Neutralizing antibodies were detected in 1 subject receiving mepolizumab. Anti-mepolizumab antibodies slightly increased (approximately 20%) the clearance of mepolizumab. There was no evidence of a correlation between anti-mepolizumab antibody titers and change in eosinophil level. The clinical relevance of the presence of anti-mepolizumab antibodies is not known.The data reflect the percentage of patients whose test results were positive for antibodies to mepolizumab in specific assays. The observed incidence of antibody positivity in an assay is highly dependent on several factors, including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.
ゾレア
Immunogenicity
No anti -therapeutic antibodies (ATAs ) against omalizumab were detected across all four CIU studies. Overall, adequate clinical pharmacology information was provided in support of this supplemental BLA.https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/UCM393855.pdf
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