Non-alcoholic steatohepatitis (NASH) is increasingly recognized as an important public health issue, and without any approved pharmaceutical treatments, drug developers have identified a potentially lucrative new market. The incidence of NASH incidence is being fed by the obesity epidemic, and more and more research is indicating it will have additional impacts on health and healthcare resources. However, despite the apparent large unmet need, there is a rather substantial stumbling block at present – low diagnosis rates.
Unfortunately, liver biopsy and histology assessment is the gold standard for diagnosis of NASH, but this is a rather unpleasant, expensive, difficult and occasionally ineffective diagnostic tool. The patient is subjected to a rather involved process of having a sample of the liver removed, with the associated risks of bleeding, infection, and even death. It can be a difficult procedure for inexperienced physicians, and even among those who are comfortable with performing it, such as hepatologists, many do not like the intervention. Consequently, it is not done frequently, with doctors preferring to use clinical experience and less invasive albeit less effective diagnostic tools. Even when a biopsy is done, the sample taken may miss the diagnosis as the histologic changes seen in NASH may not be uniformly spread across the liver. These factors, plus low awareness of NASH outside the gastroenterology specialists, have contributed to low diagnosis rates. And low diagnosis rates mean low treatment rates, which mean low revenues for new drugs.
If, as expected, novel drug prices will be high for innovative drugs meeting an important medical need, payers and insures are likely to impose cost controls and the requirement for liver biopsy could be one. But drug developers have recognized the potential hurdle and several are aiming to develop less-invasive tests that can match and hopefully surpass liver biopsy for identifying patients with NASH. NuSirt Biopharma are working in tandem with OWL Metabolomics to develop a liquid-biopsy companion diagnostic tool as part of the development program for NS-0200. Similarly, Genfit is analysing biomarkers in patients during the development of elifibranor in an attempt to replace liver biopsy and increase diagnosis rates. Independent research is also ongoing, with Cardiff University in the United Kingdom having developed a scoring system based on mass spectrometry-based profiling of plasma (see here for news story).
Although these new technologies will need to be validated against liver biopsy, we are confident that at least one of them will provide a cheaper, less-invasive, and hopefully more accurate diagnostic tool by the time new drug therapies are approved for NASH, leading to increases in diagnosis and treatment rates in the future.