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The FDA and my goat and obeticholic acid (OCA)


I recently wrote about our concern that the FDA had reset the clock on OCA, obeticholic acid, which is the first potential treatment for advancing fibrosis due to NASH. The core of my objection is that it was done without patient input.  As patients, who face potential terminal illness with no therapies, the prospect of a breakthrough drug is of vital interest.

I hope to not be unfair to the FDA here as I have not seen the actual text of their notice to cancel the planned Adcom meeting and delay a decision on OCA. That said, my understanding is that they stated that based on the data the FDA has reviewed to date, the Agency has determined that the predicted benefit of OCA based on a surrogate histopathologic endpoint remains uncertain and does not sufficiently outweigh the potential risks to support accelerated approval for the treatment of patients with liver fibrosis due to NASH

To be clear, an agreed endpoint between FDA and Intercept was a one stage reduction in fibrosis. We should also be clear about the fact that it was not useful to everyone and has a long way to go as a cure but did show a valid improvement in fibrosis.  It is the first drug to meet this threshold but it is not a clear winner and much research remains. Its position as the first to show efficacy is what makes it so important as it helps point the way to better therapy.

So why am I angry you ask? Not an ideal drug, go back to the lab and bring me something better says the FDA. Take a year, maybe two, we will be here waiting for your data.  Waiting, that's what we do they say, don't be concerned, we have our checklist right here and we are happy to get your data.

Let me tell you what this looks like to a patient.  It is important to understand just how dangerous fibrosis is. Even most patients don't understand this but what does one stage of improvement in fibrosis actually mean? Let's look at the data.


The hazard ratio is how likely you are to die compared to a healthy person. Look at stage 4 fibrosis at 10.9. A person with cirrhosis is almost 11 times as likely to die as someone without liver disease.  But look at stage 3 at 3.8.

Now ask me if a one stage reduction in fibrosis is something that I care about. Are you kidding?  What kind of measure is the FDA going to use for liver disease?  We aren't likely to suddenly "cure" NASH. This is scar tissue.  If all we could do was stop progression it would be a win for patients.  With OCA, they showed that they could reduce the problem by one stage in some patients.  As a patient, do I want that possibility? Pretend you face a potentially fatal disease and then ask yourself if that might be of value to you.

The FDA has a hard job. People live and die as a result of decisions they make.  This is a complex question and I sympathize, however, by pushing this drug development process out months to years without hearing from patients doesn't please me.

The link below is for a very brief, 2 minutes tops, survey to catch a snapshot of patient opinion.  If you haven't answered it already it would be a great help to us as we speak to the FDA.


If you are reading this and didn't see the earlier note here is a link to that post.