Please describe your clinical practice and experience with NASH/OCA.

What is your high level reaction to the Phase 3 OCA study results? link

What do you think of the pruritus side effect? Do you think it could be better managed outside of a clinical trial protocol? 

The most common adverse event reported was dose-related pruritus (19% in placebo, 28% in OCA 10 mg and 51% in OCA 25 mg). The large majority of pruritus events were mild to moderate, with severe pruritus occurring in a small number of patients (<1% in placebo, <1% in OCA 10 mg and 5% in OCA 25 mg). A higher incidence of pruritus associated treatment discontinuation was observed for OCA 25 mg (<1% in placebo, <1% in OCA 10 mg and 9% in OCA 25 mg). According to the clinical study protocol, investigator assessed severe pruritus mandated treatment discontinuation.

Please add CBAY to list of companies discussed

On Behalf of a client: Are there NASH patients warehoused for the launch?

On behalf of a client: Thoughts on the fibrosis effect size in REGENERATE, particularly given it is an ITT analysis and not a responder analysis?

On behalf of a client: How onerous will the physician education be?

On behalf of a client: Would he/she like to see future trials ran against Ocaliva or fine with placebo-controlled?

How important is fibrosis benefit versus other end points such as NASH resolution or even biomarkers such as MRI-PDFF?

On behalf of a client: Thoughts on other mechanisms such was FGF21, FGF19, PPAR, and THR? How about specifically their ability to improve fibrosis. Any other mechanisms of interest?

On behalf of a client:

• What does 11% pbo-adj. efficacy mean to you?
• Same for 32% pruritus?
  
  • 9% pruritus DC rate?!
    
  • Is OCA-induced pruritus truly manageable?
    
• Does s/he buy the story that pruritus can ameliorate over time? If so, how many can tolerate in real world since we know trials are very different?
  
  • How does a patient handle this in the real world?
    
• Thoughts on LDL increase (remember we don’t know full statin utilization plan until EASL)
  
• 3% gallstone rate did not exist in Ph2 FLINT.
  
  • Thoughts?
    
  • Why might this be occurring?
    
  • Do you see gallstones in your NASH patients naturally?
    
•  What is the commercial viability of this compound?
  
  •   How does this change with the thinking ICPT may be the only NASH F2-F3 treatment for 2-3 years?
    
  • How much does being first matter (can mention statins as an example with atorv taking the cake though was not first) in NASH?
    
•  What are your thoughts on a OCA-bezafibrate NASH FDC combo?
  

On behalf of a client: Thoughts on the pruritis? Can it be managed? Would he/she use drug holidays or dose titration? Thoughts on the pruritis data given placebo had 19% pruritis rates, seems like patients enrolled looking for the ae?

On behalf of a client: What is his/her expectation for uptake of Ocaliva? How will he/she use Ocaliva in his/her practice?

On behalf of a client: Does he/she have any concerns with Ocaliva’s liver safety in light of the update yesterday that the Placebo arm had 3 cases of Hy’s Law vs 2 on low dose vs 1 on high dose?

On behalf of a client: How would he/she hypothetical prescribe Ocaliva vs maybe a future approved THR that has no fibrosis benefit, only on NASH resolution?