WASHINGTON — In this exclusive video from Emerging Trends in Non-Alcoholic Fatty Liver Disease, Kris V. Kowdley, MD, FAASLD, of the Swedish Medical Center, Liver Care Network, Seattle, discusses clinical and regulatory design of trials for therapeutic treatments for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.
“Given the natural history of NASH, it’s unlikely that we will be able to easily demonstrate the three classic endpoints that the FDA looks for in approving a drug for clinical use, and that is how a patient feels, functions or survives,” Kowdley said. “To demonstrate clinical benefit, we need to be able to show that there are surrogate endpoints or endpoints reasonably likely to predict clinical benefit, and these include changes in liver biopsy, possible reversal or reduction in progression of fibrosis in the liver, and possible reduction in complications related to end-stage liver disease.”
Kowdley stated that because NASH is associated with obesity and hyperlipidemia, despite the fact that there is a response to lifestyle modification such as weight loss and dietary changes, less than 5% of patients have been seen to achieve and maintain 10% body weight reduction. The need, as he said, is to develop new therapies that might mitigate liver damage and reduce the progression to more advanced liver disease.
“There’s been a great deal of debate over how do you construct and conduct the clinical trials for NASH because there is a variety of moving targets; you have weight, you have diabetic control, you have lifestyle modification and exercise, and in the middle of all of this, to add a therapeutic agent poses many layers of complexity,” Kowdley said. “This is a hot area of debate, there is a lot going on, and I would invite the audience and my physician colleagues to stay tuned and follow the literature to see what new therapeutic agents available in the clinical arena in the next year or 2.”
Disclosure: Kowdley reports he is on the speakers bureau of Intercept; receives grants/research support from AbbVie, Evidera, Galectin, Gilead, Immuron, Intercept, Merck, NGM Biopharma, Novartis, Tobira and Trio Health; receives royalties from Up-To-Date; and is a consultant for Enanta, Gilead, Intercept and NGM Biopharma.