Highlights

• For something like NASH, which is very common, and the expectations for chronic disease management with multiple years of utilization, I think there will be greater price pressure, but I think what will also evolve as we have greater competition from multiple approved drugs… I think for a first drug, in the context of no competition, I think that the price range over $20,000 per year I think would be easily justified, I think in the context of 3–5 years I am quite uncertain about whether that will also hold true.
• Although you can gain approval for NASH drugs for either pathway, either NASH resolution or fibrosis improvement, in my opinion there is no question that the fibrosis improvement endpoint is far more important, and far more likely to be associated with clinical outcome improvement.
• I have to emphasize that OCA is a very imperfect and flawed drug, but I think it is the best of the bunch at least at this time, and results – 23% versus 12% for fibrosis improvement versus placebo – it is not a home run, but it is a clear effect, and it also has baggage with regards to pruritus and itching, and increases LDL cholesterol, and patients with impaired liver function, at least from the PBC literature, can be associated with an increase in liver-related events, and even liver-related deaths, and therefore it is very unlikely that OCA will be used in the cirrhosis population, they will be restricted to stage 2 and 3 at least until the Phase III results from the REVERSE trial are reported.
• I am concerned about the LDL cholesterol signal, but in the context of no competition, because we have no other options, and we need options for patients, OCA will be used. It is a concern but not a concern that will prevent clinicians and/or patients from accepting these flaws to use the drug. But in a competitive landscape, in 3–5 years where there are many other drugs potentially that will have similar and possibly superior efficacy profiles, and very likely to have better safety profiles, I think that this particular safety signal will make OCA far less attractive.