improved dose decision with comprehensive diagnostics data
TRANSCRIPT
![Page 1: Improved dose decision with comprehensive diagnostics data](https://reader030.vdocuments.net/reader030/viewer/2022020314/58e4f3bf1a28abdf698b4781/html5/thumbnails/1.jpg)
Biologics&Biosimilars Congress 2017 1
Identify the drug dose for each patient individually Challenge: Detect free antigen and free drug concentration during therapy
I´m so different, so why is the medication dose the same?
![Page 2: Improved dose decision with comprehensive diagnostics data](https://reader030.vdocuments.net/reader030/viewer/2022020314/58e4f3bf1a28abdf698b4781/html5/thumbnails/2.jpg)
Classical ELISA
TAB
Antigen
Biologics&Biosimilars Congress 2017 2
Challenge
1st AB
2nd AB HRP
![Page 3: Improved dose decision with comprehensive diagnostics data](https://reader030.vdocuments.net/reader030/viewer/2022020314/58e4f3bf1a28abdf698b4781/html5/thumbnails/3.jpg)
Classical ELISA
2nd AB HRP
TAB
Antigen
1st AB
Biologics&Biosimilars Congress 2017 3
Challenge
![Page 4: Improved dose decision with comprehensive diagnostics data](https://reader030.vdocuments.net/reader030/viewer/2022020314/58e4f3bf1a28abdf698b4781/html5/thumbnails/4.jpg)
Classical ELISA
2nd AB HRP
TAB
Antigen
1st AB
Biologics&Biosimilars Congress 2017 4
Challenge
![Page 5: Improved dose decision with comprehensive diagnostics data](https://reader030.vdocuments.net/reader030/viewer/2022020314/58e4f3bf1a28abdf698b4781/html5/thumbnails/5.jpg)
TAB Antigen
Additive Library Antigen, TAB Antigen/ TAB complex Stabilization Matrix adjustments
Plate Coating Streptavidin Poly Streptavidin Biotin …
Resources
Biologics&Biosimilars Congress 2017 5
Conjugate 1 Linker lengths …
Conjugate 2 HRP Poly HRP …
Development platform
![Page 6: Improved dose decision with comprehensive diagnostics data](https://reader030.vdocuments.net/reader030/viewer/2022020314/58e4f3bf1a28abdf698b4781/html5/thumbnails/6.jpg)
TAB
TAB- poly HRP
Capture AB
Antigen
60µl Serum
BioTeZ Algorithm
Non linear regression, Michaelis-Menten & Law of mass action
96 well plate&reader
Solution
Biologics&Biosimilars Congress 2017 6
Source: Strohner, Pavel, Stephanie Korn, Roland Buhl, and Gunther Becher. “The Recovery-
ELISA--a Novel Assay Technique to Monitor Therapy with Humanized Antibodies: The
Example of Omalizumab.” Journal of Immunoassay & Immunochemistry 34, no. 1 (2013): 83–
93. doi:10.1080/15321819.2012.683501.
The recoveryELISA® (CE marked IVD) is a combination of a sandwich ELISA and a competition ELISA
![Page 7: Improved dose decision with comprehensive diagnostics data](https://reader030.vdocuments.net/reader030/viewer/2022020314/58e4f3bf1a28abdf698b4781/html5/thumbnails/7.jpg)
Solution/Pipetting scheme
Biologics&Biosimilars Congress 2017 7
Antigen CALIBRATORS
Topping up Samples with Antigen CALIBRATORS
TAB CALIBRATORS
![Page 8: Improved dose decision with comprehensive diagnostics data](https://reader030.vdocuments.net/reader030/viewer/2022020314/58e4f3bf1a28abdf698b4781/html5/thumbnails/8.jpg)
Biologics&Biosimilars Congress 2017 8
Free Target concentration as indicator of patients drug
need.
Neutralization rate gives information's
about the ability of the drug to neutralize free
target antigens and allows prediction of
dose variations effects.
A low neutralization rate can serve as
indicator for anti-drug antibodies (ADAs).
Solution
Free Drug concentration shows individual drug
dose to meet the therapeutic window to avoid over and under
treatment. Administered drug dose and measured free drug
show individual drug absorption and drug
metabolism.
![Page 9: Improved dose decision with comprehensive diagnostics data](https://reader030.vdocuments.net/reader030/viewer/2022020314/58e4f3bf1a28abdf698b4781/html5/thumbnails/9.jpg)
Therapeutic free Drug Monitoring (TDM)
Therapeutic free Antigen Monitoring (TAM)
Therapeutic Drug/Antigen Monitoring
Solution Summary
Biologics&Biosimilars Congress 2017 9 Source: www.thenewpoundcoin.com
![Page 10: Improved dose decision with comprehensive diagnostics data](https://reader030.vdocuments.net/reader030/viewer/2022020314/58e4f3bf1a28abdf698b4781/html5/thumbnails/10.jpg)
~ 1 % of the world population are affected
Adalimumab/TNFa in RA
Biologics&Biosimilars Congress 2017 10
Source: *www.healthline.com **Sacks, Luo and Helmick, Arthritis Care Res
Observational clinical study cohort of 17 patients treated with adalimumab dose (40mg) every 14 day or according to the rheumatologist every 7 days (BOOST)
*
**
![Page 11: Improved dose decision with comprehensive diagnostics data](https://reader030.vdocuments.net/reader030/viewer/2022020314/58e4f3bf1a28abdf698b4781/html5/thumbnails/11.jpg)
Adalimumab/TNFa in RA
Biologics&Biosimilars Congress 2017 11
![Page 12: Improved dose decision with comprehensive diagnostics data](https://reader030.vdocuments.net/reader030/viewer/2022020314/58e4f3bf1a28abdf698b4781/html5/thumbnails/12.jpg)
DAS28/Boost in RA
Biologics&Biosimilars Congress 2017 12
![Page 13: Improved dose decision with comprehensive diagnostics data](https://reader030.vdocuments.net/reader030/viewer/2022020314/58e4f3bf1a28abdf698b4781/html5/thumbnails/13.jpg)
Consequences RA Study
* Key findings towards optimising adalimumab treatment: the concentration–effect curve Pouw et al Ann Rheum Dis. 2015 Mar;74(3):513-8. doi: 10.1136/annrheumdis-2013-204172.
Biologics&Biosimilars Congress 2017 13
*
![Page 14: Improved dose decision with comprehensive diagnostics data](https://reader030.vdocuments.net/reader030/viewer/2022020314/58e4f3bf1a28abdf698b4781/html5/thumbnails/14.jpg)
Consequences RA Study
Biologics&Biosimilars Congress 2017 14
Patients Brand et al Laine et al BioTeZ
Cohort Size (N) 17 1137 50
Supra-Therapeutic 18% 22% n.d.
Therapeutic Window 47% 42% n.d.
Sub-Therapeutic 35% 36% n.d.
Laine J. et al Cost-effectiveness of routine measuring of serum drug concentrations in treatment of RA patients with TNF-α blockers Targets and Therapy
Brand et al Improved dose decision in TNFa-inhibiting therapy with comprehensive diagnostics data Under review at The Journal of Rheumatology
![Page 15: Improved dose decision with comprehensive diagnostics data](https://reader030.vdocuments.net/reader030/viewer/2022020314/58e4f3bf1a28abdf698b4781/html5/thumbnails/15.jpg)
Treatment following existing guideline DAS28 as main disease indicator
Follow up study on RA patients with Horizon2020 & Innovationsfond proposals
Open label treatment including diagnostic data and real world evidence
RA Cohort
Consequences RA Study
Biologics&Biosimilars Congress 2017 15
N=260 N=260
![Page 16: Improved dose decision with comprehensive diagnostics data](https://reader030.vdocuments.net/reader030/viewer/2022020314/58e4f3bf1a28abdf698b4781/html5/thumbnails/16.jpg)
Omalizumab HRP
aIgE
IgE
Examines the underlying mechanisms of Fast vs. Slow responders to first injection of Omalizumab chronic spontaneous urticaria (CSU) patients.
IgE/Omalizumab in CSU
Biologics&Biosimilars Congress 2017 16
Source: Gericke et al J Allergy Clin Immunol. 2016 Nov 9. doi: 10.1016/j.jaci.2016.07.047. Serum autoreactivity predicts time to response to omalizumab therapy in chronic spontaneous urticaria.
![Page 17: Improved dose decision with comprehensive diagnostics data](https://reader030.vdocuments.net/reader030/viewer/2022020314/58e4f3bf1a28abdf698b4781/html5/thumbnails/17.jpg)
PCSK9/Evolocumab and Alirocumab in high LDL
Biologics&Biosimilars Congress 2017 17
Source: PCSK9 Inhibitors Pradeep Natarajan, Sekar Kathiresan DOI: http://dx.doi.org/10.1016/j.cell.2016.05.016
![Page 18: Improved dose decision with comprehensive diagnostics data](https://reader030.vdocuments.net/reader030/viewer/2022020314/58e4f3bf1a28abdf698b4781/html5/thumbnails/18.jpg)
Evolocumab- HRP
Alirocumab
PCSK9
Alirocumab- HRP
Evolocumab
PCSK9
Biologics&Biosimilars Congress 2017 18
PCSK9/Evolocumab and Alirocumab in high LDL
![Page 19: Improved dose decision with comprehensive diagnostics data](https://reader030.vdocuments.net/reader030/viewer/2022020314/58e4f3bf1a28abdf698b4781/html5/thumbnails/19.jpg)
Future Project IL6 and sIL6R
Biologics&Biosimilars Congress 2017 19
Chalaris et al Interleukin-6 Trans-Signaling and Colonic Cancer Associated with Inflammatory Bowel Disease Article in Digestive Diseases 30(5):492-9 · October 2012 DOI: 10.1159/000341698
![Page 20: Improved dose decision with comprehensive diagnostics data](https://reader030.vdocuments.net/reader030/viewer/2022020314/58e4f3bf1a28abdf698b4781/html5/thumbnails/20.jpg)
Preclinical recoveryELISA application
Biologics&Biosimilars Congress 2017 20
In Vivo Drug stability tests Drug/Antigen binding identification In early biological development stages Preclinical phases 60µl Serum ≈100µl blood are needed
Source: https://en.wikipedia.org/wiki/Laboratory_rat#/media/File:Wistar_rat.jpg
![Page 21: Improved dose decision with comprehensive diagnostics data](https://reader030.vdocuments.net/reader030/viewer/2022020314/58e4f3bf1a28abdf698b4781/html5/thumbnails/21.jpg)
Biologics&Biosimilars Congress 2017 21
For assistance and more information's please contact
Dr. Janko Brand [email protected]
Come for a chat at booth # 5
Find us next to the poster # 13
Thank you for your attention!