WHAT IS NON-ALCOHOLIC STEATOHEPATITIS (NASH)?
Non-alcoholic steatohepatitis (NASH) is a severe liver disease which affects 6-8% of adults in western industrialised nations such as the USA or countries in Europe and is on the rise in many more regions around the globe. In the USA alone, this corresponds to more than 30 million adults who have NASH and more than 14 million adults who have NASH with fibrosis. Children are also increasingly diagnosed with NASH.
Patients develop NASH as a consequence of their lifestyle. Little or no physical exercise combined with a diet, rich in saturated fat and sugar, initially leads to the storage of excessive fat in the liver (steatosis). This stage is called non-alcoholic fatty liver disease (NAFLD) and is completely reversible. However, if no changes are made to lifestyle, patients may progress to having NASH which adds inflammation, liver cell damage (ballooning) and scarring (fibrosis) to the already challenged liver. A study published in 2015 analysing the health records of over 900,000 people in the UK showed that patients with NASH have a 50% higher mortality rate compared to patients with NAFLD*. 40-50% of patients suffering from NASH progress to NASH with fibrosis. From there, progressive scarring eventually leads to irreparable cirrhosis or liver cancer, requiring a liver transplant.
Alongside diabetes and obesity, NASH is one of the major metabolic disorders of our time. While diabetes can be managed quite well with medication, there is no approved medication for NASH although the disease can lead to liver cirrhosis, liver transplantation, or liver cancer in its most severe form. The only options available to patients today are a lifestyle change, a healthier diet and increased physical activity.
It is estimated that the NASH market could reach $35bn to $40bn.
* European Association for the Study of the Liver. "Non-Alcoholic Fatty Liver Disease, Steatohepatitis: NASH linked to 50% higher death rate compared with NAFLD." ScienceDaily. ScienceDaily, 24 April 2015.
LANIFIBRANOR – OUR SOLUTION
A number of experimental treatments for NASH are being tested in clinical trials. Among those treatments lanifibranor stands out, Inventiva’s leading drug candidate for the treatment of NASH and systemic sclerosis (SSc).
Lanifibranor belongs to the class of peroxisome proliferator-activated receptor (PPAR) agonists and activates the three subtypes α, δ, and γ. PPARs are nuclear receptors responsible for the read out of certain genes involved in the regulation of metabolism and fibrotic processes. Due to its mechanism of action, lanifibranor addresses all the key features of NASH: inflammation, steatosis, ballooning, and importantly fibrosis. This aspect of treating fibrosis is crucial as NASH patients with severe fibrosis are exposed to an increased risk of developing irreversible cirrhosis*.
Lanifibranor is currently being tested in a Phase IIb clinical trial called NATIVE. The trial is open and recruiting patients. Headline results are expected in the second half of 2019.
In addition, Dr. Kenneth Cusi, Chief of the Division of Endocrinology, Diabetes & Metabolism in the Department of Medicine at the University of Florida, Gainesville, has selected lanifibranor for an investigator-initiated Phase II trial to evaluate the efficacy and safety of lanifibranor on intrahepatic triglycerides and hepatic insulin sensitivity in type 2 diabetic patients with non-alcoholic fatty liver disease (NAFLD). The trial is planned to commence enrolment in the second half of 2018. For a recording of a presentation on the study by Dr. Cusi, Pierre Broqua, CSO and co-founder of Inventiva, and Jean-Louis Abitbol, Chief Medical Officer of Inventiva, please click here.
HOW IS non-alcoholic steatohepatitis (NASH) DIAGNOSED?
NASH is a silent disease which means that many affected patients are not aware that they are suffering from NASH. They do not experience pain nor do they necessarily have abnormal liver enzymes. The American Association for The Study of Liver Diseases (AASLD) therefore recommends generally testing patients who are at risk of having NASH*. Those patients typically suffer from diabetes, obesity, cardiovascular disease and carry additional risk factors such as age or ethnicity.
Because liver enzymes are normal in 60% of NASH patients, a liver biopsy is required to properly diagnose NASH.
An initiative has been launched, supported by Inventiva, to educate people and raise awareness about NASH: The NASH Education Program.
WHAT IS A LIVER BIOPSY?
A liver biopsy is a procedure performed in hospital or outpatient centres under local anaesthetic. The entire procedure takes a few minutes and is generally regarded as very safe. A small incision is made in the upper abdomen and a fine needle is inserted into the liver to remove a small amount of liver tissue. The patient will take a couple of hours to recover after the procedure and will then be allowed to go home. The liver sample is then analysed in a laboratory to look for changes to the appearance of the tissue indicating the presence or absence of NASH. The specialists will look for steatosis, inflammation, liver cell injury, fibrosis, and architectural remodelling which will provide information regarding the stage and severity of the disease.
Currently, there are no non-invasive tests available for a reliable diagnosis.