Therapeutic Product Immunogenicity Community

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  • 1.  Sustaining ADA

    Posted 04-19-2025 15:20

    Hello TPI Community colleagues,

    does anyone have publication references for sustaining ADA? In one of my lectures I have used an IL-3 example in mice, but I am interested in expanding that with more examples, especially clinical examples. Published manuscripts and product inserts alike can be useful.

    Thanks!



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    Gopi Shankar, Ph.D., MBA, FAAPS
    AAPS Member-at-Large/Board Member
    VP, Biologics Development Sciences, Janssen R&D, LLC (Johnson & Johnson)


    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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  • 2.  RE: Sustaining ADA

    Posted 04-21-2025 13:16

    Hi Gopi, the best examples I know of are for metreleptin and tofersen. For metreleptin, Chan et al 2016 Clinical Endocrinology, has some nice ADA kinetic profiles and for tofersen there is language in the label indicating that presence of ADA appeared to decrease clearance. 

    Thanks

    Michael



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    Michael Partridge
    Senior Director
    Regeneron Pharmaceuticals
    Tarrytown NY
    [email protected]

    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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    Original Message


  • 3.  RE: Sustaining ADA

    Posted 04-24-2025 13:09

    See article: Development of a population pharmacokinetic model to characterize the pharmacokinetics of intrathecally administered tominersen in cerebrospinal fluid and plasma, Y. Yamamoto et.al. CPT Pharmacometrics Syst Pharmacol. 2023;12:1213–1226.



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    Eric David
    Scientific Director
    Biogen
    Cambridge MA
    [email protected]

    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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    Original Message


  • 4.  RE: Sustaining ADA

    Posted 04-24-2025 13:24

    Thank you, Eric.

    Cheers!

     

    *** Gopi ***

     




    Original Message


  • 5.  RE: Sustaining ADA

    Posted 04-21-2025 14:37

    Gopi

    my recollection is either G-CSF or (I think more likely) GM-CSF.  There was a webinar a few years ago that Sue Richards, me and someone else put together for AAPS that if memory serves had a slide showing a sustaining ADAs-must have had a ref for it.  If I can dig that out of my files, I'll send it.

    regards

    Eric



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    Eric Wakshull Ph.D
    Consultant
    Eric Wakshull Consulting
    Santa Fe NM
    [email protected]

    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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    Original Message


  • 6.  RE: Sustaining ADA

    Posted 04-22-2025 09:22

    Another example of decreased clearance in the presence of ADA is somatrogon (Ngenla). The prescribing information describes a magnitude of 26% decrease in CL/F in the presence of ADA. 



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    Joan Korth-Bradley Pharm.D., Ph.D., FAAPS
    Distinguished Scientist
    Vivpro
    Lower Gwynedd PA
    [email protected]

    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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    Original Message


  • 7.  RE: Sustaining ADA

    Posted 04-22-2025 12:16

    Hi Gopi,

    For me, the best examples of sustaining ADA activity are ADA binding to small molecules and essentially, making them behave like large molecules. Lixisenatide is a good example (https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208471Orig1s000OtherR.pdf) where ADA increased PK by about 10 fold. It's probably the case for other GLP-1 agonists but they are not nearly as immunogenic as lixisenatide, and the effect on PK is harder to detect. ADA against anti-sense oligonucleotides such as mipomersen, inotersen or eplontersen lead to increased Ctrough concentrations although with no observable effect on AUC. This is mentioned in the product inserts and a paper  by Rosie Yu et al provides more details for inotersen  "Immunogenicity Assessment of Inotersen, a 2'-O-(2-Methoxyethyl) Antisense Oligonucleotide in Animals and Humans: Effect on Pharmacokinetics, Pharmacodynamics, and Safety. Nucleic Acid Ther. 2020 Oct;30(5):265-275. doi: 10.1089/nat.2020.0867.

    I hope this is useful.

    Best regards,

    Robert



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    Robert J. Kubiak, PhD
    Director, Head of Bioanalytical Science
    Third Arc Bio
    [email protected]

    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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  • 8.  RE: Sustaining ADA

    Posted 04-22-2025 13:56

    @Robert Kubiak, @Eric Wakshull, @Joan Korth-Bradley, @Susan Irvin and @Michael Partridge, I am grateful for your prompt responses, which have indeed expanded my toolkit of drug-sustaining ADA. Thanks!



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    Gopi Shankar, Ph.D., MBA, FAAPS
    AAPS Member-at-Large/Board Member
    VP, Biologics Development Sciences, Janssen R&D, LLC (Johnson & Johnson)


    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
    ------------------------------

    Original Message