NAFLD and NASH biomarker qualification in the LITMUS consortium ? Lessons learned

Daniel Guldager Kring Rasmussen; Quentin M. Anstee; Richard Torstenson; Bruno Golding; Scott D. Patterson; Clifford Brass; Paresh Thakker; Stephen Harrison; Andrew N. Billin; Detlef Schuppan; Jean-Fran?ois Dufour; Anneli Andersson; Ioan Wigley; Elizabeth Shumbayawonda; Andrea Dennis; Corinna Schoelch; Vlad Ratziu; Carla Yunis; Patrick Bossuyt; Morten Asser Karsdal

doi:https://doi.org/10.1016/j.jhep.2022.11.028

NAFLD and NASH biomarker qualification in the LITMUS consortium ? Lessons learned

Daniel Guldager Kring Rasmussen, Quentin M. Anstee, Richard Torstenson, Bruno Golding, Scott D. Patterson, Clifford Brass, Paresh Thakker, Stephen Harrison, Andrew N. Billin, Detlef Schuppan, Jean-Fran?ois Dufour, Anneli Andersson, Ioan Wigley, Elizabeth Shumbayawonda, Andrea Dennis, Corinna Schoelch, Vlad Ratziu, Carla Yunis, Patrick Bossuyt, Morten Asser Karsdal

Research output: Contribution to journal › Review article › Academic › peer-review

12 Citations (Scopus)

Abstract

Biomarkers have the potential to accelerate drug development, as early indicators of improved clinical response, to improve patient safety, and for personalised medicine. However, few have been approved through the biomarker qualification pathways of the regulatory agencies. This paper outlines how biomarkers can accelerate drug development, and reviews the lessons learned by the EU IMI2-funded LITMUS consortium, which has had several interactions with regulatory agencies in both the US and EU regarding biomarker qualification in patients with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Sharing knowledge of such interactions with the scientific community is of paramount importance to increase the chances of qualification of relevant biomarkers that may accelerate drug development, and thereby help patients, across disease indications. A qualified biomarker enables a decision to be made that all understand and support in a common framework.

Original language	English
Pages (from-to)	852-865
Number of pages	14
Journal	Journal of Hepatology
Volume	78
Issue number	4
Early online date	2023
DOIs	https://doi.org/10.1016/j.jhep.2022.11.028
Publication status	Published - Apr 2023

Keywords

EMA
FDA
accelerated approval
context of use
drug development tool
health authorities
health authority
regulatory interactions

Access to Document

https://doi.org/10.1016/j.jhep.2022.11.028

Cite this

Rasmussen, D. G. K., Anstee, Q. M., Torstenson, R., Golding, B., Patterson, S. D., Brass, C., Thakker, P., Harrison, S., Billin, A. N., Schuppan, D., Dufour, J.-F., Andersson, A., Wigley, I., Shumbayawonda, E., Dennis, A., Schoelch, C., Ratziu, V., Yunis, C., Bossuyt, P., & Karsdal, M. A. (2023). NAFLD and NASH biomarker qualification in the LITMUS consortium ? Lessons learned. Journal of Hepatology, 78(4), 852-865. https://doi.org/10.1016/j.jhep.2022.11.028

@article{871ca94c94164f328b7f6b22f2b25ae7,

title = "NAFLD and NASH biomarker qualification in the LITMUS consortium ? Lessons learned",

abstract = "Biomarkers have the potential to accelerate drug development, as early indicators of improved clinical response, to improve patient safety, and for personalised medicine. However, few have been approved through the biomarker qualification pathways of the regulatory agencies. This paper outlines how biomarkers can accelerate drug development, and reviews the lessons learned by the EU IMI2-funded LITMUS consortium, which has had several interactions with regulatory agencies in both the US and EU regarding biomarker qualification in patients with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Sharing knowledge of such interactions with the scientific community is of paramount importance to increase the chances of qualification of relevant biomarkers that may accelerate drug development, and thereby help patients, across disease indications. A qualified biomarker enables a decision to be made that all understand and support in a common framework.",

keywords = "EMA, FDA, accelerated approval, context of use, drug development tool, health authorities, health authority, regulatory interactions",

author = "Rasmussen, {Daniel Guldager Kring} and Anstee, {Quentin M.} and Richard Torstenson and Bruno Golding and Patterson, {Scott D.} and Clifford Brass and Paresh Thakker and Stephen Harrison and Billin, {Andrew N.} and Detlef Schuppan and Jean-Fran?ois Dufour and Anneli Andersson and Ioan Wigley and Elizabeth Shumbayawonda and Andrea Dennis and Corinna Schoelch and Vlad Ratziu and Carla Yunis and Patrick Bossuyt and Karsdal, {Morten Asser}",

note = "Funding Information: This study has been supported by the LITMUS (Liver Investigation: Testing Marker Utility in Steatohepatitis) consortium funded by the Innovative Medicines Initiative (IMI2) Program of the European Union under Grant Agreement 777377, which receives funding from the EU Horizon 2020 programme and EFPIA. This communication reflects the view of the LITMUS Consortium and neither IMI nor the European Union and EFPIA are liable for any use that may be made of the information contained herein. Funding Information: DGKR and MAK are employees and stock owners of Nordic Bioscience A/S. QMA has grants or contracts with Abbvie, AstraZeneca, Boehringer Ingelheim, Glympse Bio, Intercept, Novartis, Pfizer, consulting fees on behalf of Newcastle University from Alimentiv, Akero, AstraZeneca, Axcella, 89Bio, Boehringer Ingelheim, Bristol Myers Squibb, Galmed, Genfit, Genentech, Gilead, GlaxoSmithKline, Hanmi, HistoIndex, Intercept, Inventiva, Ionis, IQVIA, Janssen, Madrigal, Medpace, Merck, NGMBio, Novartis, Novo Nordisk, PathAI, Pfizer, Poxel, Resolution Therapeutics, Roche, Ridgeline Therapeutics, RTI, Shionogi, Terns, and payment or honorario from Fishawack, Integritas Communications, Kenes, Novo Nordisk, Madrigal, Medscape, Springer Healthcare. RT is an employee of AstraZeneca. BG is an employee of Roche Diagnostics International AG. SDP and ANB are employees and stock owners of Gilead Sciences, Inc. CB receives consulting fees from TEVA and is a stock owner of Merck, Novartis and Organon. PT is an employee of Takeda Development Center Americas, Inc. SH has received grants or contracts from Akero Therapeutics, Inc., Axcella Health, Inc., Cirius Therapeutics, Inc., CiVi Biopharma Inc., Cymabay Therapeutics, Inc., Enyo Pharma S.A, Galectin Therapeutics, Inc., Galmed Research & Dev. LTD., Genfit Corp, Gilead Sciences, Inc., Hepion Pharmaceuticals, Inc., Hightide Therapeutics, Inc., Intercept Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Metacrine Inc., NGM Biopharmaceuticals Inc., Northsea Therapeutics, Novartis Pharmaceuticals Corp, Novo Nordisk, Poxel, Sagimet Biosciences, Viking Therapeutics, Inc, consulting fees from AgomAB, Akero Therapeutics, Inc., Alentis Therapeutics AG, Alimentiv, Inc., Altimmune, Axcella Health, Inc., Boston Pharmaceuticals, B Riley FBR Inc., BVF Partners LP, Cohbar, Inc. Canfite, Corcept Therapeutics, Inc, Cymabay Therapeutics, Inc., Echosens North America Inc., Enyo Pharma S.A, Fibronostics, Foresite Labs, LLC, Fortress Biotech, Inc., Galectin Therapeutics, Inc., Genfit Corp, GNS, Hepion Pharmaceuticals Inc., Hightide Therapeutics, Inc., HistoIndex PTE LTD, Inipharm, Intercept Pharmaceuticals, Inc., Ionis, Kowa Research Institute, Inc., Madrigal Pharmaceuticals, Inc., Medpace, Inc. Metacrine Inc., Microba, NGM Biopharmaceuticals INC., Northsea Therapeutics B.V, Novo Nordisk, Nutrasource, Perspectum Diagnostics, Piper Sandler, Poxel, Prometic, Pharma SMT LTD, Ridgeline, Sagimet Biosciences, Sonic Incytes Medical Corp, Terns Inc., Viking Therapeutics, Inc, participates on a data safety monitoring board or advisory board of 89 Bio, Akero Therapeutics, Inc., Altimmune, Arrowhead, Axcella Health, Inc., Chronwell, CiVi, Cymabay Therapeutics, Inc., Echosens North America Inc., Foresite Labs, LLC, Galectin Therapeutics, Inc., Galmed Research & Dev. LTD, Genfit Corp, Gilead Sciences, Inc, Hepion Pharmaceuticals, Inc., Hightide Therapeutics, Inc., HistoIndex PTE LTD, Indalo, Intercept Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Medpace Inc., Metacrine Inc., NGM Biopharmaceuticals., Northsea Therapeutics B.V, Novartis Pharmaceuticals, Novo Nordisk, PathAI, Poxel, Prometic Pharma SMT LTD, Ridgeline, Sagimet Biosciences, Sonic Incytes Medical Corp, Terns Inc., Theratechnologies, and is a stock owner of Akero Therapeutics, Inc., Chronwell Inc., Cirius Therapeutics, Inc, Galectin Therapeutics, Inc., Genfit Corp, Hepion Pharmaceuticals Inc., HistoIndex PTE LTD, Metacrine Inc., NGM Biopharmaceuticals., Northsea Therapeutics B.V, Sonic Incytes Medical Corp. JFD receives payment or honorary for speaking and teaching from Bayer, Bristol-Myers Squibb, Intercept, Gilead Sciences, Novartis, Roche and is on an advisory board for Alentis, Astra-Zeneca, Bayer, Bristol-Myers Squibb, Enyo, Esai, Falk, Genfit, Gilead Sciences, Intercept, Inventiva, Ipsen, Lilly, Madrigal, Merck, Novartis, Novo-Nordisk, Roche. AA, IW, ES and AD are employees of Perspectum. CS is an employee of Boehringer Ingelheim Pharma GmbH & Co. KG. VR receives consulting fees from Novo Nordisk, Terns, Madrigal, Enyo, Poxel, Bristol Myers Squibb, Intercept Pharmaceuticals, NGM Pharmaceuticals and Merck, and has received research grants from Gilead Sciences and Intercept Pharmaceuticals. CY is an employee and stock owner of Pfizer. All other authors have no disclosure in relation to the manuscript. Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2023",

month = apr,

doi = "https://doi.org/10.1016/j.jhep.2022.11.028",

language = "English",

volume = "78",

pages = "852--865",

journal = "Journal of Hepatology",

issn = "0168-8278",

publisher = "Elsevier",

number = "4",

}

Rasmussen, DGK, Anstee, QM, Torstenson, R, Golding, B, Patterson, SD, Brass, C, Thakker, P, Harrison, S, Billin, AN, Schuppan, D, Dufour, J-F, Andersson, A, Wigley, I, Shumbayawonda, E, Dennis, A, Schoelch, C, Ratziu, V, Yunis, C, Bossuyt, P & Karsdal, MA 2023, 'NAFLD and NASH biomarker qualification in the LITMUS consortium ? Lessons learned', Journal of Hepatology, vol. 78, no. 4, pp. 852-865. https://doi.org/10.1016/j.jhep.2022.11.028

TY - JOUR

T1 - NAFLD and NASH biomarker qualification in the LITMUS consortium ? Lessons learned

AU - Rasmussen, Daniel Guldager Kring

AU - Anstee, Quentin M.

AU - Torstenson, Richard

AU - Golding, Bruno

AU - Patterson, Scott D.

AU - Brass, Clifford

AU - Thakker, Paresh

AU - Harrison, Stephen

AU - Billin, Andrew N.

AU - Schuppan, Detlef

AU - Dufour, Jean-Fran?ois

AU - Andersson, Anneli

AU - Wigley, Ioan

AU - Shumbayawonda, Elizabeth

AU - Dennis, Andrea

AU - Schoelch, Corinna

AU - Ratziu, Vlad

AU - Yunis, Carla

AU - Bossuyt, Patrick

AU - Karsdal, Morten Asser

N1 - Funding Information: This study has been supported by the LITMUS (Liver Investigation: Testing Marker Utility in Steatohepatitis) consortium funded by the Innovative Medicines Initiative (IMI2) Program of the European Union under Grant Agreement 777377, which receives funding from the EU Horizon 2020 programme and EFPIA. This communication reflects the view of the LITMUS Consortium and neither IMI nor the European Union and EFPIA are liable for any use that may be made of the information contained herein. Funding Information: DGKR and MAK are employees and stock owners of Nordic Bioscience A/S. QMA has grants or contracts with Abbvie, AstraZeneca, Boehringer Ingelheim, Glympse Bio, Intercept, Novartis, Pfizer, consulting fees on behalf of Newcastle University from Alimentiv, Akero, AstraZeneca, Axcella, 89Bio, Boehringer Ingelheim, Bristol Myers Squibb, Galmed, Genfit, Genentech, Gilead, GlaxoSmithKline, Hanmi, HistoIndex, Intercept, Inventiva, Ionis, IQVIA, Janssen, Madrigal, Medpace, Merck, NGMBio, Novartis, Novo Nordisk, PathAI, Pfizer, Poxel, Resolution Therapeutics, Roche, Ridgeline Therapeutics, RTI, Shionogi, Terns, and payment or honorario from Fishawack, Integritas Communications, Kenes, Novo Nordisk, Madrigal, Medscape, Springer Healthcare. RT is an employee of AstraZeneca. BG is an employee of Roche Diagnostics International AG. SDP and ANB are employees and stock owners of Gilead Sciences, Inc. CB receives consulting fees from TEVA and is a stock owner of Merck, Novartis and Organon. PT is an employee of Takeda Development Center Americas, Inc. SH has received grants or contracts from Akero Therapeutics, Inc., Axcella Health, Inc., Cirius Therapeutics, Inc., CiVi Biopharma Inc., Cymabay Therapeutics, Inc., Enyo Pharma S.A, Galectin Therapeutics, Inc., Galmed Research & Dev. LTD., Genfit Corp, Gilead Sciences, Inc., Hepion Pharmaceuticals, Inc., Hightide Therapeutics, Inc., Intercept Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Metacrine Inc., NGM Biopharmaceuticals Inc., Northsea Therapeutics, Novartis Pharmaceuticals Corp, Novo Nordisk, Poxel, Sagimet Biosciences, Viking Therapeutics, Inc, consulting fees from AgomAB, Akero Therapeutics, Inc., Alentis Therapeutics AG, Alimentiv, Inc., Altimmune, Axcella Health, Inc., Boston Pharmaceuticals, B Riley FBR Inc., BVF Partners LP, Cohbar, Inc. Canfite, Corcept Therapeutics, Inc, Cymabay Therapeutics, Inc., Echosens North America Inc., Enyo Pharma S.A, Fibronostics, Foresite Labs, LLC, Fortress Biotech, Inc., Galectin Therapeutics, Inc., Genfit Corp, GNS, Hepion Pharmaceuticals Inc., Hightide Therapeutics, Inc., HistoIndex PTE LTD, Inipharm, Intercept Pharmaceuticals, Inc., Ionis, Kowa Research Institute, Inc., Madrigal Pharmaceuticals, Inc., Medpace, Inc. Metacrine Inc., Microba, NGM Biopharmaceuticals INC., Northsea Therapeutics B.V, Novo Nordisk, Nutrasource, Perspectum Diagnostics, Piper Sandler, Poxel, Prometic, Pharma SMT LTD, Ridgeline, Sagimet Biosciences, Sonic Incytes Medical Corp, Terns Inc., Viking Therapeutics, Inc, participates on a data safety monitoring board or advisory board of 89 Bio, Akero Therapeutics, Inc., Altimmune, Arrowhead, Axcella Health, Inc., Chronwell, CiVi, Cymabay Therapeutics, Inc., Echosens North America Inc., Foresite Labs, LLC, Galectin Therapeutics, Inc., Galmed Research & Dev. LTD, Genfit Corp, Gilead Sciences, Inc, Hepion Pharmaceuticals, Inc., Hightide Therapeutics, Inc., HistoIndex PTE LTD, Indalo, Intercept Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Medpace Inc., Metacrine Inc., NGM Biopharmaceuticals., Northsea Therapeutics B.V, Novartis Pharmaceuticals, Novo Nordisk, PathAI, Poxel, Prometic Pharma SMT LTD, Ridgeline, Sagimet Biosciences, Sonic Incytes Medical Corp, Terns Inc., Theratechnologies, and is a stock owner of Akero Therapeutics, Inc., Chronwell Inc., Cirius Therapeutics, Inc, Galectin Therapeutics, Inc., Genfit Corp, Hepion Pharmaceuticals Inc., HistoIndex PTE LTD, Metacrine Inc., NGM Biopharmaceuticals., Northsea Therapeutics B.V, Sonic Incytes Medical Corp. JFD receives payment or honorary for speaking and teaching from Bayer, Bristol-Myers Squibb, Intercept, Gilead Sciences, Novartis, Roche and is on an advisory board for Alentis, Astra-Zeneca, Bayer, Bristol-Myers Squibb, Enyo, Esai, Falk, Genfit, Gilead Sciences, Intercept, Inventiva, Ipsen, Lilly, Madrigal, Merck, Novartis, Novo-Nordisk, Roche. AA, IW, ES and AD are employees of Perspectum. CS is an employee of Boehringer Ingelheim Pharma GmbH & Co. KG. VR receives consulting fees from Novo Nordisk, Terns, Madrigal, Enyo, Poxel, Bristol Myers Squibb, Intercept Pharmaceuticals, NGM Pharmaceuticals and Merck, and has received research grants from Gilead Sciences and Intercept Pharmaceuticals. CY is an employee and stock owner of Pfizer. All other authors have no disclosure in relation to the manuscript. Publisher Copyright: © 2022 The Author(s)

PY - 2023/4

Y1 - 2023/4

N2 - Biomarkers have the potential to accelerate drug development, as early indicators of improved clinical response, to improve patient safety, and for personalised medicine. However, few have been approved through the biomarker qualification pathways of the regulatory agencies. This paper outlines how biomarkers can accelerate drug development, and reviews the lessons learned by the EU IMI2-funded LITMUS consortium, which has had several interactions with regulatory agencies in both the US and EU regarding biomarker qualification in patients with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Sharing knowledge of such interactions with the scientific community is of paramount importance to increase the chances of qualification of relevant biomarkers that may accelerate drug development, and thereby help patients, across disease indications. A qualified biomarker enables a decision to be made that all understand and support in a common framework.

AB - Biomarkers have the potential to accelerate drug development, as early indicators of improved clinical response, to improve patient safety, and for personalised medicine. However, few have been approved through the biomarker qualification pathways of the regulatory agencies. This paper outlines how biomarkers can accelerate drug development, and reviews the lessons learned by the EU IMI2-funded LITMUS consortium, which has had several interactions with regulatory agencies in both the US and EU regarding biomarker qualification in patients with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Sharing knowledge of such interactions with the scientific community is of paramount importance to increase the chances of qualification of relevant biomarkers that may accelerate drug development, and thereby help patients, across disease indications. A qualified biomarker enables a decision to be made that all understand and support in a common framework.

KW - EMA

KW - FDA

KW - accelerated approval

KW - context of use

KW - drug development tool

KW - health authorities

KW - health authority

KW - regulatory interactions

UR - http://www.scopus.com/inward/record.url?scp=85146859027&partnerID=8YFLogxK

U2 - https://doi.org/10.1016/j.jhep.2022.11.028

DO - https://doi.org/10.1016/j.jhep.2022.11.028

M3 - Review article

C2 - 36526000

SN - 0168-8278

VL - 78

SP - 852

EP - 865

JO - Journal of Hepatology

JF - Journal of Hepatology

IS - 4

ER -

NAFLD and NASH biomarker qualification in the LITMUS consortium ? Lessons learned

Abstract

Keywords

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