The importance of the NAFLD activity score and the STAM™ model’s clinical relevance
In this issue, we would like to introduce the NAFLD activity score (NAS), which is one of the main endpoints used in the development of drug candidates for NASH, and the role it plays in our proprietary STAM™ model.
But, first, what is NAS and how does it relate to the study of NASH?
The guidelines given by the Food and Drug Administration (FDA) for the development and evaluation of NASH therapeutics provide the following three points:
- The ultimate goal of NASH treatment is to slow the progress of, halt, or reverse disease progression and improve clinical outcomes.
- Because of the slow progression of NASH and the time required to conduct a trial that would evaluate clinical endpoints such as progression to cirrhosis or survival, the FDA recommends sponsors consider the following liver histological improvements [NAS] as endpoints reasonably likely to predict clinical benefit to support accelerated approval under the regulations.
- Resolution of steatohepatitis on overall histopathological reading and no worsening of liver fibrosis on NASH CRN fibrosis score. Resolution of steatohepatitis is defined as absent fatty liver disease or isolated or simple steatosis without steatohepatitis and a NAS score of 0–1 for inflammation, 0 for ballooning, and any value for steatosis; Resolution of fatty hepatitis by comprehensive histopathologic evaluation and absence of worsening liver fibrosis by NAS. Resolution of fatty hepatitis is defined as absence of fatty liver disease or isolated or simple lipidosis without fatty hepatitis, with NAS scores of 0 to 1 for inflammation, 0 for ballooning, and any value for lipidosis (Noncirrhotic Nonalcoholic Steatohepatitis With Liver Fibrosis: Developing Drugs for Treatment).
The above sections are just a small part of the guidelines provided by the FDA, however, as noted in 3, NAS is an important criterion and indispensable endpoint in the ongoing endeavor to discover an effective treatment for NASH.
As the guidelines point out, NAS involves quantifying and scoring the three specific histological abnormalities of NASH, inflammation (accumulation of immune cells), ballooning, and lipid droplets, via biopsy.
Our STAM™ model is an innovative NASH model in which these three features of NAS can be observed.
To put it another way, our model accurately reflects the pathophysiology of NASH patients and has a high clinical correlation.
Would you like to advance the development of your NASH therapeutic candidate in a drug evaluation study using the STAM™ model?
If you are interested, but would first like to learn more about the accuracy of our model, we have included two links below to studies published by our clients Novartis and Enanta Pharmaceuticals. Both companies tested their molecule in the STAM™ model as a possible drug candidate for NASH, and both entered into, and are currently in, clinical trial.
Please also feel free to contact us if you would like more information on NAS in the STAM™ model, basic data such as tissue profiles, or more information regarding our services.
We are always happy to hear from clients, whether new or returning, so that we can help them to reach new heights in their drug development journey.
■The guidelines given by FDA
■About our STAM™ model
■References on nonclinical testing of NASH drug candidates in STAM™ model.
Farnesoid X Receptor Agonist (Enanta Pharmaceuticals)： Ping et al., Liver Int. 2020 Jul;40(7):1655-1669
Tropifexor (Novartis)： Hernandez et al., Hepatol Commun. 2019 May 17;3(8):1085-1097