Bioanalytical Community

Dear all,

A colleague reached out requesting published case studies that describe development failure of a given biologic due to either unmanageable immunogenicity, or poor PK/bioavailability/lack of exposure, or inability to scale up manufacturing sufficiently. Since much of this isn't published, I am putting out a collective call for citations that list one of these as the reason development discontinued.

Joleen

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Joleen White Ph.D.
AAPS 2023 Global Health Community Past Chair
Bioanalytical 101 Course Development
Head of Bioassay Development and Operations
Gates Medical Research Institute
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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Hi Joleen,
The case of a bioengineered FVII comes to mind. It was developed by Novo Nordisk but discontinued in Ph3 due to immunogenicity, probably to neo-epitopes. The post-hoc assessment is published:  Lamberth et al., Sci. Transl. Med. 9; eaag1286 (2017).
Hope this helps,
Lena

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Lena Hofer
Spark Therapeutics
Philadelphia 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:
Sent: 01-03-2023 11:17
From: Joleen White
Subject: Case studies for discontinued biologic development

Dear all,

A colleague reached out requesting published case studies that describe development failure of a given biologic due to either unmanageable immunogenicity, or poor PK/bioavailability/lack of exposure, or inability to scale up manufacturing sufficiently. Since much of this isn't published, I am putting out a collective call for citations that list one of these as the reason development discontinued.

Joleen

------------------------------
Joleen White Ph.D.
AAPS 2023 Global Health Community Past Chair
Bioanalytical 101 Course Development
Head of Bioassay Development and Operations
Gates Medical Research Institute
Cambridge MA
[email protected]

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

I think this is a great and very timely question as biological modalities evolve (way) beyond Mab and humanized proteins and peptides introducing foreign epitopes through multi-specific fusions, linkers, etc. Also, what is a good ref on bioanalytical strategy for PK measurement in the presence of high levels of ADA? Taking into consideration the ideal of measuring bioactive drug that correlates with safety/efficacy/PD.

"Unmanageable immunogenicity" also begs the question of what are the mitigation strategies related to treatment (not bioanalytical) that have been successfully employed?

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Heather Myler Ph.D.
Executive Director
PPD Laboratories
Richmond VA
[email protected]

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

Original Message:
Sent: 01-03-2023 11:17
From: Joleen White
Subject: Case studies for discontinued biologic development

Dear all,

A colleague reached out requesting published case studies that describe development failure of a given biologic due to either unmanageable immunogenicity, or poor PK/bioavailability/lack of exposure, or inability to scale up manufacturing sufficiently. Since much of this isn't published, I am putting out a collective call for citations that list one of these as the reason development discontinued.

Joleen

------------------------------
Joleen White Ph.D.
AAPS 2023 Global Health Community Past Chair
Bioanalytical 101 Course Development
Head of Bioassay Development and Operations
Gates Medical Research Institute
Cambridge MA
[email protected]

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