NASH (Non-Alcoholic Steatohepatitis) is a rising disease that is sweeping the population. It is a terminal diagnosis that currently requires a liver transplant, either as a treatment for liver cancer or from disease progression. Clinical development is searching for a chronic medication that can either reverse the pathology of the liver or arrest the development of the disease. There are currently no approved treatments available for NASH other than liver transplant, and the rate of diagnosis is increasing.
To mark International NASH Day, we spoke with Tristan Baldwinson, Director of Project Delivery at PRA. We asked him what NASH is, how we can raise more awareness around it, and what our experience and expertise is here at PRA with regard to the research on NASH.
For people who haven’t heard the term "NASH", tell us what it is.
TB: Many of us know about the cardiovascular disease risks associated with poor diet and exercise. Many people are also familiar with the comorbid links to metabolic diseases such as diabetes. These links can lead to fatty deposits building up in arteries (atherosclerosis) and the potential for blood clots, which can cause a heart attack or stroke.
We can think of NASH as the effects of these same inflictions on the liver. Over time, the buildup of fat in the cells of the liver (hepatocytes) can cause inflammation and cell death, which leads progressively to scar tissue formation (fibrosis). In some patients, this progresses to liver cirrhosis and an increased probability of liver cancer (hepatocellular carcinoma or HCC).
Part of the challenge with NASH is that it’s hard to detect, particularly in the early stages. It tends to go unnoticed by the patient. But with levels of obesity, hypertension, diabetes, and pre-diabetes on the rise—especially in westernized countries—it is feared that the prevalence of fatty liver disease is on the rise. If we don’t have an effective way to combat it, NASH may soon be a leading (if not THE leading) cause of liver transplants.
What is your / our experience with and expertise in NASH?
TB: PRA has been at the leading edge of NASH clinical research and fortunate enough to work on many NASH clinical trials. We’ve conducted over 100 hepatology trials over the last five years. We supported five of seven Phase III studies launched to date, and a greater number of Phase I and Phase II studies as well.
Through our experience with these trials, PRA has gained an exceptional understanding of the challenges facing our clients, regulators, and healthcare professionals in this indication. I head up a team of hepatologists/gastroenterologists and operational experts focused on developing treatments for NASH and fatty liver disease.
What should the public know about NASH?
TB: It takes years for initial fatty liver disease to progress to its more severe form of NASH. Research is ongoing into the mechanisms by which this occurs, as well as into other risk factors. From an environmental and genetic perspective, however, one clear risk factor to developing the disease is poor diet and lack of exercise. Small lifestyle adjustments can change the course of this disease and improve outcomes for patients.
If you or someone you know are concerned they might have fatty liver disease, talk to your physician. You can discuss whether you might be at risk and whether it’s appropriate for further evaluation, as well as what lifestyle changes would suit you.
What kind of treatments are available for people with NASH today? How far have we come? Where do we still need to go?
TB: As it stands, there is no marketed product specifically for NASH, despite the growing concern over the burden to healthcare systems both now and in the future.
We may start to see treatments emerging later this year, but we’ve also seen several molecules fail even at later stages of development. There’s still a lot to learn. We need to know more about how the disease progresses, what reliable biomarkers can be used to access the effectiveness of new treatments, and figure out ways to make treatments less invasive and burdensome for our participants.
Single agents that focus on a particular molecular target can show a degree of efficacy with regards to not only histological changes in the disease course but also in clinical outcomes. This means that future treatments will need to involve drug combinations alongside more holistic lifestyle changes.
TB: Do you have any supporting materials around PRA’s NASH expertise?
A quarter of PRA’s clinical operations and project delivery staff possess hepatology experience. We’re also fortunate to have 12 inhouse board-certified hepatologists/gastroenterologists and a team of global drug development directors who support our clients in the effective design and operational delivery of NASH trials.
We’ve supported over 30 NASH studies in the last five years across more than 1950 clinical research sites and 30 countries. We understand the challenges our clients face when developing their assets in NASH, whether it’s related to the competitive landscape, the burden of trial participation to patients, biological material logistics, or the ongoing development to trial design requirements from regulatory.