Submission of initial Qualification Package to FDA – 11th October 2023

After a period spanning more than six years, we have today successfully submitted the initial Qualification Package (QP) to the Food and Drug Administration (FDA). This comprehensive submission includes PRO-C3, ADAPT, and the FAST score, with the context of use ‘Diagnostic Enrichment’. Such an achievement stands as a testament to the collective endeavours of the entire LITMUS consortium, embracing the realms of clinical science, biomarker science, and regulatory initiatives. This submission has been presented to the Center for Drug Evaluation and Research (CDER) as part of the biomarker qualification program, specifically under the Drug Development Tool: Qualification Plan.

The goal of the LITMUS project has been to develop and validate highly accurate blood tests and imaging techniques that will allow doctors and researchers to rapidly and easily diagnose the severity of patients’ disease and monitor changes in patients’ livers for Metabolic dysfunction-associated steatohepatitis (MASH), previously known as non-alcoholic steatohepatitis (NASH).

This submission was done in collaboration with NIMBLE, demonstrating how big consortia can work together to forward science, assist in drug development and help patients.

LITMUS is funded by the European Union’s Innovative Medicines Initiative 2 (IMI2) Joint Undertaking under grant agreement No. 777377. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. LITMUS acknowledges the FNIH NIMBLE Consortium (Non-Invasive Biomarkers Of Metabolic Liver Disease (NIMBLE) for contributing to this work with clinical data from their ultrasound study which is used to assess the repeatability and reproducibility of FAST score. The Foundation for the National Institutes of Health (FNIH) creates and leads alliances and public-private partnerships that advance breakthrough biomedical discoveries and improve the quality of people’s lives.

We sincerely wish to thank all stakeholders and patients that have participated in the European NAFLD (MASLD) Registry, without whom this would not have been possible.

On behalf of all of LITMUS,

The Project Executive team:

  • Quentin M. Anstee, Newcastle University
  • Carla Yunis, Pfizer Inc.
  • Patrick Bossuyt, AMC Amsterdam
  • Vlad Ratziu, Institute of Cardiometabolism And Nutrition
  • Detlef Schuppan, University Medical Center Mainz
  • Jörn M. Schattenberg, University Medical Center Mainz
  • Toni Vidal-Puig, University of Cambridge
  • Stephen Harrison, University of Oxford
  • Morten Asser Karsdal, Nordic Bioscience
  • Diana Julie Leeming, Nordic Bioscience
  • Maria Manuela Tonini, Integrated Biobank of Luxembourg
  • David Wenn, iXscient
  • Jeremy Magnanensi, Genfit
  • Kevin Duffin, Eli Lilly and Company
  • Mette Skalshøi Kjaer, Novo Nordisk
  • Richard Torstenson, AstraZeneca
  • Clifford Brass, Resolution Therapeutics

Other key people:

  • Michael Pavlides, University of Oxford
  • Daniel G. K. Rasmussen, Nordic Bioscience
  • Neel Ingemann Nissen, Nordic Bioscience
  • Céline Fournier-Poizat, Echosens

Key NIMBLE participants:

  • Arun Sanyal
  • Tania Kamphaus
  • Roberto Calle

October 2016:

The European IMI2-funded LITMUS consortium has reached a major milestone in the biomarker qualification process by having our letter of intent (LOI) accepted by the U.S. Food and Drug Administration (FDA). With this LOI, LITMUS aims to qualify non-invasive biomarkers to enable simpler diagnosis and better treatment for patients with non-alcoholic steatohepatitis (NASH). The FDA supports and encourages the study of non-invasive biomarkers for NASH, where better tools to diagnose and treat patients are needed. The acceptance allows LITMUS to submit a qualification plan, providing a more comprehensive description of the steps the requestor will take to provide the necessary supportive data for biomarker qualification. At the same time LITMUS has also finalized two scientific advice interactions with the European Medicines Agency (EMA).

Members of the WP7 Regulatory team involved in creating the LOI are as follows:

  • Elisabeth Erhardtsen (Nordic Bioscience)
  • Richard Torstenson (Abbvie)
  • Daniel Guldager Kring Rasmussen (Nordic Bioscience)
  • Morten Karsdal (Nordic Bioscience)
  • Guido Hanauer (Takeda)
  • Camilla Bertelsen (Novo Nordisk)
  • Julia Brosnan (Pfizer)
  • Vlad Ratziu (Hôpital Pitié-Salpêtrière, Paris)
  • Patrick Bossuyt (Amsterdam University Medical Centre)
  • Quentin M. Anstee (Newcastle University)


A pioneering European research project aims to lead to new diagnostic tests to assess patients with non-alcoholic fatty liver disease (NAFLD) and identify those most at risk for developing severe inflammation and liver scarring.

Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS) funded by the European Innovative Medicines Initiative 2 Joint Undertaking, brings together clinicians and scientists from prominent academic centres across Europe with companies from the European Federation of Pharmaceutical Industries and Associations (EFPIA). Their common goals are developing, validating and qualifying better biomarkers for testing NAFLD.

The €34 million project is co-ordinated by Newcastle University, working closely with the lead EFPIA partner, Pfizer Ltd. LITMUS will include 47 international research partners based at leading international universities and some of the world’s largest pharmaceutical companies.

Affecting 20 – 30 % of the population worldwide, NAFLD is caused by a build-up of fat in the liver cells, which leads to inflammation, scarring of the liver and ultimately cirrhosis. It is strongly linked to obesity and type 2 diabetes.

Although many people have NAFLD, less than one in 10 will come to harm as a result1. The challenge is to identify those people that will be most severely affected and are going to progress to liver cirrhosis or cancer so that appropriate care can be provided earlier. At present this requires a liver biopsy, which can only be done in specialist hospitals, so there is a need for better diagnostic tools.

Professor Quentin Anstee, from Newcastle University’s Institute of Cellular Medicine and Consultant Hepatologist at Newcastle Hospitals NHS Foundation Trust, is co-ordinating the LITMUS consortium.

He said: “Non-alcoholic fatty liver disease is already the most common underlying cause of liver transplant in the USA and, with the obesity epidemic in Europe, we are very close behind.

“LITMUS will unite clinicians and academic experts from centres across Europe with scientists from the leading pharmaceutical companies, all working together to develop and validate new highly-accurate blood tests and imaging techniques that can diagnose the severity of liver disease, predict how each patient’s disease will progress and monitor those changes, better or worse, as they occur.

“Lack of easy and accurate diagnostic tests means that many patients go undiagnosed until late in the disease process. It has also held-back efforts to develop new medical treatments for NAFLD. Availability of better diagnostic tests will help us to target care at an early stage of disease to the people who are going to be most severely affected. It will also help us to develop more effective medical treatments for NAFLD and to run the clinical trials that the regulatory agencies need so that they can licence these medicines to be prescribed by doctors.”

Professor Chris Day, Vice-Chancellor and President, Newcastle University who is himself a Consultant Hepatologist with an international reputation and part of the research team, added: “Tackling Non-alcoholic fatty liver disease is a major public health challenge and the award of such a large grant from the EU, allowing us to bring together pharma and academia in this way, gives us real hope of making significant advances in the diagnosis and treatment of this increasingly common and often devastating disease.”

Julia Brosnan, Senior Director of External Collaborations & Scientific Alliances, Pfizer, who also serves as the industry project lead for LITMUS, said: “This is an exciting project and we look forward to working with the other LITMUS partners to develop new diagnostic tests for NAFLD, which is too often undiagnosed in patients. We hope the results of this project will help change that.”

This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777377. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.

Living with NAFLD – Yvonne’s story

Yvonne Gray, 62, was diagnosed with NAFLD in 2011. A retired headteacher who lives in Fulwell, Sunderland, she is now a governor of the national adult liver patient support group, LIVErNORTH:

“I do consider myself really fortunate in that it was by chance my liver disease was eventually diagnosed, when my “mildly abnormal” liver function tests were picked up by a consultant treating me for a Vitamin D deficiency and he then referred me to a hepatologist.

“By the time I was referred to the Freeman Hospital Liver Unit in Newcastle I had Non-Alcoholic Fatty Liver Disease, specifically NASH, Stage 3 Liver Disease with significant fibrosis.

“It is interesting that even now my liver function tests are still presenting as ‘mildly abnormal’, thereby not appearing to trigger any major cause for concern. However, my two liver biopsies say something totally different.

“It is exciting to hear about this new collaboration. I would be delighted if there could be a simple blood test. The alternative, a liver biopsy, can involve a stay in hospital, is uncomfortable and can be painful.”

NAFLD – the facts

A healthy liver should contain little or no fat, however, it is thought that 1 in every 3 people in Europe has some degree of NAFLD, where there is an excessive amount of fat accumulation in the liver. While this doesn’t always cause harm, it can develop into an inflammatory form of the condition called steatohepatitis (NASH) that in turn causes fibrous scar tissue to form in the liver and leads to serious liver damage including cirrhosis in some patients. It can also increase the risk of cancer in the liver, heart attack, and stroke.

Follow LITMUS on Twitter: @LITMUS_IMI

This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777377.

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This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 777377. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. Visit IMI.

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