Some comment about FDA and new drugs for #NASH, also I need your help with a letter we will be sending to FDA. 8 questions I need your help!

[nash2]

surveymonkey.com/r/L28VFRM

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. They are supposed to be listening to patients but in this case we have had no opportunity to comment and the more patients who take the survey the better as we argue for our right to speak.

surveymonkey.com/r/L28VFRM

Thanks

Wayne

[Splodge60]

Hi Nash 2

Most of your comments are highly technical, as, where I come from in my journey with NASH, is a background of “No Treatment at all’ after being diagnosed with NASH by biopsy in 2003. As a result, after 15 years I was sent back to the same Consultant (a Gastroenterologist). Because of his ‘wait and see’ policy it was January 2019 when I had my very first Fibroscan (despite significant deterioration in my health). I had to push for it as well. By that time I had completely bi-passed Fibrosis and got the diagnosis of Cirrhosis. The drug you mention was and is, to my knowledge, never an option in the UK. Please tell me if someone knows differently. THe Consultant still has a cautious attitude and I just keep hearing that I don’t need to worry as I am stable. Please can I be educated on what docs mean by stable. NASH has affected almost every organ in my body. There’s lots more to this story but I just feel that what you are saying makes a lot of sense, but I fear more simplified layman’s terms may get your message across to the largely interested but uninitiated sufferers of NASH, when you use medical jargon and acronyms. I don’t mean to offend you but I feel your audience may be wider with such an approach xx. I too am angry, annoyed, very emotional and furious that my Primary GP put on my medical notes that I only had months to live. All I have had from these people are blood tests, Ultrasound on Abdomen, CT scans and complaints to their seniors for my diagnosis (of Cirrhosis) and (months to live) were found by myself on the Patient Portal. For Cirrhosis, it took me 4 months to get to speak to ANY medic and for the Prognosis, I have to wait till 20th August (from 8th June) to speak to anyone. Meanwhile my body is not happy and my history of depression has reared its ugly head again, accompanied by severe anxiety. Good luck with your quest in the US!!

[nash2 Partner in reply to Splodge60]

Sorry to learn that your journey has been so difficult. Sadly, it happens that way far too often. So many docs aren't concerned about liver disease. It happened to me and is what caused me to become a patient advocate. I appreciate your comments. I have no knowledge how things work in the UK but I've heard stories like yours before. So sad really.

There are lots of places that people can get a simpler explanation of things. Most sites, pardon the description, "dumb their information down". I've been told to write to a 5th grade audience. I find I can't do that. The details are too important and if I do use a term that someone finds unfamiliar they do have the ability to look it up and learn more about this disease. I try not to write in full science mode but I think understanding the disease is the most important thing.

Thanks

Wayne