Biomarkers in NASH Drug Development: Using Cytokeratin 18 as a Secondary Endpoint in Clinical Trials

Life Sciences, Clinical Trials, Pharmaceutical, Biomarkers,
  • Monday, October 22, 2018

Non-alcoholic fatty liver disease (NAFLD) is a medical condition characterized by the build-up of fat in the liver. NAFLD has a spectrum that ranges from steatosis and non-alcoholic steatohepatitis (NASH) to fibrotic NASH and cirrhosis. The prevalence of NAFLD worldwide is reported to be 20-35%, and it is strongly connected to the global epidemic of obesity and type 2 diabetes. In the United States NAFLD is the most common form of chronic liver disease and a leading indication for liver transplantation. There are currently no approved drug therapies for NAFLD or NASH, and many clinical trials are underway to address this unmet need for pharmacologic treatment options.

Liver biopsy is still considered the “gold standard” for diagnosis of NASH, and histological endpoints are currently required by the FDA for approval of NASH drugs. However, liver biopsy has many drawbacks, including sampling error, cost, risk of complications, and patient acceptability. Because of these limitations and concerns regarding liver biopsy, non-invasive biomarkers are urgently needed not just to identify subjects with NASH, but also to determine their response to novel therapeutic agents.

Markers of hepatic injury or cell death such as cytokeratin 18 (CK18 or K18) and its caspase-cleaved fragment, cCK18, have been suggested as endpoints for early clinical drug trials where histological assessments are not feasible. The M30 Apoptosense® ELISA is a specific and reliable tool to measure the concentration of cCK18 fragments. Biomarker assays used for drug development should be validated and run in a bioanalytical lab based on the context of use of the biomarker. Celerion has validated the M30 Apoptosense® ELISA for use as a secondary endpoint in NASH clinical trials.


Naim Alkhouri, MD, Associate Professor of Medicine, Division of Gastroenterology, Adult & Pediatric Hepatologist, Liver Transplant Program, Texas Liver Institute

Dr. Alkhouri was most recently Assistant Professor of Medicine at the Cleveland Clinic Digestive Disease and Surgery Institute and Director of the Metabolic Liver Disease Clinic. He completed his medical degree at the University of Damascus in Syria before completing his internal medicine and pediatric residency at Albert Einstein Medical Center in Philadelphia. Dr. Alkhouri completed his pediatric gastroenterology, hepatology and nutrition fellowship at Cleveland Clinic and an adult transplant hepatology fellowship at the Digestive Disease and Surgery Institute, Cleveland Clinic. Dr. Alkhouri received the American College of Gastroenterology Junior Faculty Development Award to study the analysis of breath volatile organic compounds to diagnose nonalcoholic fatty liver disease. He also received the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Fellow Research Award for his prospective evaluation of the pediatric NAFLD fibrosis index and ELF markers in children with fatty liver disease. Dr. Alkhouri has over 100 publications and presents his work at both national and international medical conferences. Dr. Alkhouri is a member of several professional organizations, including the American Association for the Study of Liver Disease, the European Association for the Study of the Liver, American College of Gastroenterology, and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. His specialty interests include nonalcoholic fatty liver disease, viral hepatitis, autoimmune hepatitis, alpha 1 antitrypsin deficiency, and liver transplantation.

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Sabina Paglialunga, PhD, Associate Director, Scientific Affairs, Celerion

Dr. Sabina Paglialunga is the Associate Director, Scientific Affairs at Celerion ( where she provides scientific support for early clinical studies, client consultation and subject matter expertise for metabolic disease drug development programs. Her areas of expertise include the obesity, type 2 diabetes and nonalcoholic fatty liver disease indications. Sabina joined Celerion in April 2015 and previously held the position of Metabolic and Pharmacodynamic Specialist.

Sabina received her Ph.D. from McGill University in Canada in the department of Biochemistry. Her training also includes three Postdoctoral Fellowships at the University of Waterloo and University of Guelph in Canada, and Maastricht University in the Netherlands. Over her research career, Sabina has contributed to more than 30 peer-review articles and continues to publish on topics of metabolic diseases, pharmacodynamic tools and regulatory aspects of drug development.

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Sumit Kar, Lead Scientist, Biomarkers, Celerion

Sumit Kar is the Lead Scientist for Biomarkers in Bioanalytical Services at Celerion ( In this role, he is responsible for the development of immunoassays for biomarkers and biosimilars. Sumit received his B.S. from Creighton University and has over ten years of experience in molecular biology and disease pathophysiology. He has authored five peer-reviewed publications and numerous posters and presentations on the topics of bioanalysis, biomarkers, and biosimilars. He joined Celerion in 2017 and has an intimate understanding of the regulatory requirements for biomarkers in drug development.

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Who Should Attend?

VPs, Directors, and Managers from biopharmaceutical companies and contract research organizations working within NASH clinical research

What You Will Learn

Join this webinar for a discussion of NASH biomarkers, including:

  • A brief introduction of NAFLD and NASH and the role of CK18 in these diseases
  • An overview of CK18 in NASH clinical trials
  • Bioanalytical validation of cCK18 for drug development

Xtalks Partner

Diapharma Group, Inc.

Diapharma is a US-based distributor of specialty diagnostic and research assays for the fields of hemostasis & thrombosis, hepatology, pharmaceutical biosafety, and environmental toxicology. With a team of dedicated technical and scientific product managers, Diapharma is able to bring leading assays from the EU to the US market. Our portfolio of biomarker assays includes the M30 Apoptosense® (cCK18) and M65® (CK18) ELISA kits from VLVbio. For research use only in the U.S. and Canada.

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