GS-9674 Phase 3 Study (YOU WANT TO READ THIS)

Over the past two years, I have been participating in Gilead’s GS-9674 PSC study, which involves taking an experimental drug now labeled as Cilofexor. Cilofexor is a “nonsteroidal FXR agonist”, and its function is supposedly to reduce bile production in the liver. As we know, it’s the backup of bile from PSC which causes damage to our livers over time. During the study, I was also allowed to continue to take Urso, as they are studying the combination of Cilofexor and Urso used together to reduce bile buildup in the liver.

The study is coming to a close, and the good news is that they are now extending the study to current participants under what they call “open label”. This means that everyone who was involved with the study, including those given the placebo, will be allowed to continue taking the experimental medication for an additional two years. The clinician I have met with over the past two years said that the fact that they are allowing open label continuation is really good news, and that, had the study not been successful, they would not have done this, and it could be a sign that they will seek FDA approval of the drug.

I would like to share my experience with the study with everyone here, in hopes that maybe it provides some hope that there may be a treatment available in the future for this terrible disease.

As part of the study, I was required to have a liver biopsy done both at the beginning of the study, as well as the end of the study, which I just had done about a month ago. The specialist who read the biopsies said in his report that “ the one from 2019 showed bridging fibrosis, while the one from 2021 showed portal fibrosis. There was a regression, which suggests perhaps improvement”.

To be honest, I feel that taking the study drug over these past two years provided significant benefit. During my time with PSC, I have had these predicable “episodes” every 3-4 months, which starts with sharp RUQ pain, followed in the next couple of days by itching, heartburn, and sometimes nausea. These symptoms always occur in tandem, so it definitely appears to be the PSC. While on the study medication, I noticed a significant reduction in both the number of these episodes, and, when they did occur, the symptoms were less severe than before taking the study medication. While it is always possible I received the placebo, I had significant itching when first starting the medication, which is a side effect of the medication, and the clinician told me it was very likely I was receiving the drug and not the placebo. Thankfully the itching resolved as my body got used to the drug. My Fibroscans also improved as well, which were taken at periodic intervals throughout the study, so all good signs.

Additionally, my liver enzymes were stable the entire time, using the combination of Urso and Cilofexor.

Hopefully we will see the full results of the study published in the next year or so, but I wanted to share my experience here. I will post again as I progress further into the open label portion of the study.

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great news!!!
I’m so glad you’re giving us such nice news. I’m really looking forward to the official results with the hope that there will be a functional treatment on PSC soon. many reports suggest that the new drugs in phase 3 will really help.:heart:

Please keep us posted. How exciting, hopefully there will be some help for this horrible disease.
Thank you so much for sharing.
God bless
:crossed_fingers::crossed_fingers::crossed_fingers::blush::blush::blush::blush:

Hello Steve:
Thanks for sharing. this is encouraging news.
tell me: were you taking the Urso and Cilofexor before starting the trial medicine?
Mark R.

Wonderful news.

Hi Mark,

Cilofexor is the study medication, so I have only been taking this drug during the study.

I had been taking Urso for about two years before the study and continue to take it now.

Thanks for that clarification.
Keep us posted!
Hopes and prayers are with you.
Mark R

Hello Steve, I was just wondering if this new drug helped with your liver numbers? I have been on URSO for 5 years at least and my liver numbers are still high. I’m told my bile ducts aren’t releasing the bile into the liver. I feel great and live a normal life but every one of my liver panel numbers are high, especially the Alk Phosphatase which is in the 450 range. Just wondering if this might be an option for me, though I live in Green Bay and there probably isn’t a trial study nearby. thx for an answer.

I too have been on the trial, with my last visit before beginning open label to take place in January. I have asked that I be informed of whether I was on the drug or placebo after unmasking and the study is complete. I believe I was on the placebo. No increased pruritis following the while after starting on the drug and while my LFT (primarily ALP) numbers decreased a bit early on, they rose back subsequently. I also had a sharp and prolonged rise in numbers coupled with intense pruritis, a year and a few months after starting the trial.

I could be wrong but I recall that the participation criteria was for PSC patients with a low MELD score rather than those with advanced progression of the disease. That doesn’t mean it won’t be available to others but it might not be as effective.

Criteria for the trial in the screenshot FYI

I did actually get a phone call yesterday from the study nurse who advised that they were required to notify trial partipants of a mouse study that showed increased risk of hepatocellular cancer. I am not overly concerned personally as I understand that often nice receive much higher doses of drugs in research. I also wonder why this is coming forth now as I thought mouse studies precede human clinical trials. I have asked for reference to the study and will post if I get it.

Thanks for the post

Oh yes, I was on URSO during the whole of the trial and had been on it since 2017, shortly after initial diagnosis.

LJ,
You say your liver numbers are remaining high. I would assume you also mean your bilirubin as well. The bile ducts don’t release bile into the liver, the liver releases bile into the bile ducts and out into your gut. Have you had an ERCP recently to check for strictures in the bile ducts? If not, I’d ask about that. Usually, that will get the bile flowing again. Also, have you checked your MELD score lately? Go to this link and check it against your most recent labs. MELD Calculator - OPTN

Mark

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Hi,

I had been on Urso for two years before starting the study, and the Urso had normalized my liver numbers. So, for me, its hard to tell. We may have to wait until Gilead releases the results of the study to see if it benefited others.

I was told that they were not able to tell you whether you were on the drug or the placebo, but maybe I am mistaken.

At least once you go to open label, you will be certain you are getting the medication and not the placebo. Be sure to let us know if it helps.

How were your liver biopsies? Did they give you the results?

After the unmasking and when the evaluation is complete which could be a few years down the line.

I had asked and was told it should be possible.

It can’t be until the study is complete and published.

I haven’t had my second biopsy or MRI yet (will be done likely in Jan) but I will get the results. I do have info from earlier in the study though. Can post when available

Thx for the reply Mark…My total bilirubin number is 1.2 so not terrible right…I tried to do the MELD calculator like you suggested but the serum sodium (mEq/L) box in the calculator was different from my tests result numbers which read…Sodium 135-145 mmol/L … I did use that number (140) to do the test and the MELD score came back at 7. I really don’t understand this disease and whats considered bad numbers or how serious things are. I’m going for a Fibroscan next week and then probably a MRCP after that. My last MRCP was in 2018. I also had a liver biospy in 2018. I have never had a ERCP. Thanks for taking the time to reply .

Hi, with regards to blood chemistry, the numbers my hepatologist is most concerned with are Alkaline Phosphatase (ALP) and Bilirubin. I have attached my 2017 liver panel, which shows the standard ranges for the various blood chemistry markers (at least for my lab).

Since you are going in for an MRCP, I would ask them to compare and contrast the new one with the 2018 MRCP, so that you can understand how the disease is progressing. Areas of concern are usually when they mention new areas showing signs of stricture and beading, that were not present on the previous MRCP.

Regarding Fibroscans, I have had probably 6-8 of these over the past 3 years or so, and I noticed the scores tend to fluctuate a lot. The clinician I work with told me they are not the most accurate tests, but can still be a good tool, expecially if you have a few of them that you can kind of get a feel for where things stand.

Hello Steve…your liver panel numbers look ok to me. Not far off from the standards. Even with these numbers your doctor was concerned that your PSC was acting up?

Those were from 2017 lol. They are actually much better now due to urso and cilofexor.

Before I started with urso and cilofexor, they were much much higher. ALP got up to around 250 if I recall and ALT 272 so they were definitely abnormal.

Do you also have IBD? What are you taking for that?