NASH KOL Insight Interview #1
$599.00
NASH KOL Insight Interview #1
$599.00
The prevalence data would suggest that in the US population about 30% of our population has fatty liver or NAFLD and of those 25% may have NASH and of those patients with NASH 25% percent may have fibrosis and progress to cirrhosis. It’s almost a pyramid effect, there may be 80 million Americans walking around with NAFLD, but to climb up to the top of the pyramid and develop cirrhosis would be about 5% of that total population, but that’s still significant because that would mean that the prevalence of cirrhosis [due to NASH] will exceed that of hepatitis C-related cirrhosis ten-fold
Publisher: Biomedtracker
Published:
20 February 2014
Number of pages:
9
Formats:
Pdf
- Description
- Contents
KOL Highlights Include:
- 10-12% of the US population will have some form of NAFLD, 10-15% of those patients will have NASH, and a quarter of NASH patients will progress to cirrhosis. The NASH market is a moving target as the obesity and diabetes epidemic continues.
- Simtuzumab (GILD) is targeting advanced patients with cirrhosis and will be a costly and difficult IV treatment, but it is targeted to patients waiting for a transplant with no other options. Hepatic venous pressure is a clinically meaningful endpoint.
- The FLINT trial of INT-747, OCA (ICPT) could lead to approval in NASH, but KOL would like to see further stratification of patients who would benefit from treatment or a more global benefit like weight loss. High LDL may be treatable or may narrow the approval label depending on overall cardiovascular picture.
- NIDDK is running a trial for Procysbi (RPTP) in adolescents. This is an important NASH target population, and there will likely trials of OCA in this patient population following the positive FLINT data.
- GR-MD-02 (GALT) is a galectin-3 inhibitor with an interesting mechanism showing reversal of fibrosis in animals models and the clinical trials will be targeting more advanced NASH patients.
- Highlights
- We are interested in discussing NASH, particularly current treatment paradigms, new drug development, and clinical trial designs. Could you describe your current practice?
- Could you walk us through a diagnostic assessment patients with NAFLD or NASH?
- You are currently researching non-invasive diagnostics, right?
- Fibroscan is an approved device for non-invasive imaging, could that be used for staging or detecting progression of disease?
- Would MRI with increased resolution be useful for staging?
- Can you briefly go over the incidence and prevalence of NASH as well as the subpopulation of advanced NASH patients with cirrhosis?
- How much of the rise in HCC is due to Hepatitis C versus NASH?
- There was a GILD trial in HCC patients, would you expect any regression of the tumor itself after treatment with a direct-acting antiviral (DAA)?
- There was a session on clinical endpoints sponsored by the FDA that you attended. Could you tell me what was discussed in that session?
- Looking at recent NASH clinical trials, we’ve seen a few different endpoints. At the more advanced stages of disease, hepatic venous pressure?
- It gets trickier in the broader NASH population?
- In some clinical trials, we’ve seen the NAFLD Activity Score (NAS) as an endpoint, for example in adolescent cohorts as they’re trying to avoid liver biopsy. Also we’ve seen a 2 point improvement in NAS leading to the stopping the trial for efficacy. Was that endpoint discussed as a potential surrogate for clinical benefit?
- So we haven’t seen details from these clinical trials, and we will not see outcomes for a long time. Are there any other measures that might make compounds more attractive for approval, like weight loss, insulin resistance, etc?
- What are the best biomarkers in development that might correlate with clinical outcomes? If you’re improving LDL, you’re probably improving cardiovascular health or at least your risk for future cardiac events?
- Well, weight loss also has long term benefits to patients.
- So what were some of the biomarkers discussed that may be used in trial designs or as surrogate clinical endpoints for early stage NASH patients?
- There are a few drugs in development for NASH that are also in development for primary biliary cirrhosis (PBC), could you discuss the potential surrogate biomarker endpoints necessary for accelerated approval there?
- Can we discuss mechanisms of action and targets of interest in early-stage and advanced NASH, either clinically or preclinically that might be more attractive than others either targeting fibrosis deposition? For example, monoclonocal antibodies targeting fibroblast deposition.
- Fat/steatosis is also a component of the NAS score?
- So, it is possible to see a two point decrease in NAFLD activity score due to just fat loss in the liver?
- When looking at clinical data, will there be specific risk stratification factors you expect to be explored? For example diabetics vs non-diabetics.
- What is your current treatment regimen, is there anything in addition to diet and exercise modification?
- With bariatric surgery do you see improvements in NAFLD or NASH?
- Have you seen advances with gastric sleeves?
- Are people benefiting from treatment with obesity drugs with respect to inflammatory markers?
- Do you recommend weight loss drugs as an option for obese patients with NAFLD/NASH?
- You mentioned treating lipid levels in your patients. In one of the clinical trials, elevated lipid levels (100-130) were observed in some patients. Is that concerning?
- Is there a lipid threshold level at which you become concerned?
- As you are currently under a confidentiality agreement and can’t discuss specific compounds in detail, are there any preclinical targets of interest that you can speak of that look promising?
- Do the animal models of NAFLD translate well from bench to bedside?
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