Treatment with Sovaldi anf Riba for 48 weeks

[Upbeat]

After 4 weeks the virus is undetectable. I was told everone doing this como is undetectable after 4 weeks.  I was somewhat shocked that they wanted me to go out for 48 weeks or transplant which ever came first.  I asked if any trials went farther than 24 and they said no. I know my situation is not typical but I think 48 weeks may be over kill.  Does anyone have any info they can shed on this?

[Upbeat]

Thanks again for your imput.  I understand  the trial you were in and the purpose. I wonder how many people would have gone on to SVR after 48 weeks if no transplant was givin?  

[HectorSF]

Thanks nan & pooh! You stated exactly what happened to me in our trial. The trial that allowed the FDA to approve Sovaldi + ribavirin for those with HCC.

"An Open-Label Study to Explore the Clinical Efficacy of Sofosbuvir With Ribavirin Administered Pre-Transplant in Preventing Hepatitis C Virus (HCV) Recurrence Post-Transplant"

Purpose
The primary objective is to determine if the administration of a combination of sofosbuvir (GS-7977; PSI-7977) and ribavirin (RBV) to HCV-infected subjects with hepatocellular carcinoma (HCC) meeting the MILAN criteria prior to undergoing liver transplantation for up to 24 weeks can prevent post-transplant re-infection as determined by a sustained post-transplant virological response (HCV RNA < LLoQ) at 12 weeks post-transplant.

ClinicalTrials.gov Identifier: NCT01559844

First received: March 5, 2012
Last updated: August 30, 2013
Last verified: August 2013
History of Changes

http://www.clinicaltrials.gov/ct2/show/NCT01559844?term=sofosbuvir+HCC&rank=1
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A few related fun facts about Sovaldi and Ribavirin.
* 99% of people treating with Sovaldi are undetectable by week 4. So RVR and eRVR is ancient history. It is irrelevant now.

* There is NO viral breakthrough any more. Like RVR it is an obsolete term when talking about Sovaldi treatment. In other words everyone becomes undetectable by week 4 and remains undetectable until treatment is stopped.

"he trial that Hector participated in had him taking Sofosbuvir + Ribavirin for 48 weeks. He was undetected from week 4 on.  Unfortunately, he was not able to get a liver transplant during that period and treatment ended at 48 weeks. A month later, he had a viral breakthrough before transplant. After he was transplanted, the new liver was infected with the virus. "

All absolutely correct.
My hepatologist tried to get Gilead to treat me beyond 48 weeks but they won't do it. They said no one had ever treated beyond 48 weeks and they wouldn't risk it for safety reasons. Since I was removed off the transplant waiting-list because my cancer became untransplantable (beyond the criteria to be eligible for transplant), when I finished the treatment I had no chance of transplant. So I stopped at 48 weeks. I had a PCR test one month after stopping and I had a viral load. I relapsed. That is how people fail Sovaldi treatment since they all become undetectable and there are no breakthroughs It is the only way to fail treatment. Therefore I infected my donor liver (which did NOT have HCV when it was connected to my blood system).

Here is the interim data from my trial....(taken from the Sovaldi label)

"An interim analysis was conducted on 61 subjects who received SOVALDI and ribavirin; 45 subjects had HCV genotype 1; 44 subjects had a baseline CPT score less than 7 and all subjects had a baseline unadjusted MELD score ≤14. Of these 61 subjects, 41 subjects underwent liver transplantation following up to 48 weeks of treatment with SOVALDI and ribavirin; 37 had HCV RNA < LLOQ at the time of transplantation. Of the 37 subjects, the post-transplant virologic response (pTVR) rate is 64% (23/36) in the 36 evaluable subjects who have reached the 12 week post-transplant time point. The safety profile of SOVALDI and ribavirin in HCV-infected subjects prior to liver transplantation was comparable to that observed in subjects treated with SOVALDI and ribavirin in Phase 3 clinical trials."

"the post-transplant virologic response (pTVR) rate is 64%"

NOTE this is NOT SVR. That wasn't the purpose of the trial. The purpose of this treatment is to be on treatment the day a person has their transplant. The trial data shows that if that is done there will be no recurrence 12 weeks post transplant. This the donor liver is not infected with the virus.

In practical terms what are the implications. I am not sure if everyone knows this but for those still infected with the virus post transplant there is about a 20% - 30% chance that the patient with develop cirrhosis of their donor liver with about 5 years. Once cirrhosis is established, the annual risk of hepatic decompensation defined as the development of ascites, hepatic encephalopathy or variceal bleeding, is 42%  Which means that it shortens the survival time for people who have had transplants due to the virus leading to cirrhosis and the need for transplant. Since about half of all liver transplants are need by those infected with hep C this has a huge impact of many people post transplant. Even a very small percentage of patients can develop fibrosing cholestatic hepatitis C (FCH). Recurrence post transplant is a major issue facing post transplant patients.
Luckily because of the progress being made with treatment this issue should not be such a major one as it has been until now.

I should add that the reason that a post transplant person can develop cirrhosis and End-Stage Liver Disease so rapidly as compared to the normal 20-40 year time line is that we are immunosuppressed so that we don't reject a "foreign" liver. I guess I should also add that many transplant centers do not do second transplants and even if the person can get a second transplant outcomes are poor generally.

As far as 48 weeks being over-kill...as I said before the purpose is to be treating when you get a transplant. It has been know for years that if a person is undetectable going into transplant they have a chance to not have recurrence. This is true with peg-interferon and ribavirin as well. But many patients are too ill to tolerate peg-IFN and ribavirin as they approach transplant.

I failed this treatment after 47 weeks of being undetectable. That is a very long time being undetectable and still have the virus come back. Although I must add that I was only one of us 61. We don't have the data yet on others who treated for 48 weeks and what happened to them. We are all different and I am a outlier in many respects. "So your mileage my vary." Hopefully so if you end up in my position.

Probably what you might be wondering... is about side effects over 48 weeks. Compared to peg-IFN and ribavirin it had almost no relationship. I couldn't even tell that I was treating for the fist 4 weeks. I felt nothing different. It was only because I saw my viral load test results that I even knew I was taking a placebo. I had some headaches early in treatment  than disappeared and a continual increasing fatigue over the 48 weeks. All and all it was a easy treatment to do and I felt like I could have done another 12 or 24 weeks if Gilead had allowed me to.
And just to repeat because people still persist with some fantasy about ribavirin causing anemia by just looking at ...the reality is quite different I never became anemic over 48 weeks never mind 12 or 24. If you read the trial results few people do when combined with Sovaldi.
The trial data for Sovaldi and Ribavirin for 24 weeks was 6% !!!
For 12 week trials 8%.

The way people talk you would think most become anemic like the old triple treatment. One one is ever going to do triple treatment with telaprevir or boceprevir again. That is history now for anyone starting treatment.

I guess that is about it from me.
Any question about the treatment?

Howie  

[nan535]

Thanks for the correction on relapse vs viral breakthrough, Pooh.

I am just wondering what the data from this limited trial shows. Unfortunately, Hector was not able to get transplanted within the 48 week window.  Is there information on the other participants who did get transplanted during the 48 week period? Was the treatment successful in preventing recurrent Hep C in the new liver?

Nan

[pooh55811]

Hector had a relapse, not a viral breakthrough. A relapse occurs if the person is UND at end of treatment and then becomes DET again at some point after the person has finished the medications. A viral breakthrough occurs if the person becomes UND during Tx and then becomes DET again while still on Tx.

If you read my post above you will see Hector's own words, from his previous post. I quoted what he said about the trial he was in and what he said about himself. Plus, there is a link to his entire post, which explains everything very well.  

[nan535]

Hi Upbeat

In order for the virus to not infect the new liver, a patient would have to be cured of the virus before transplant.

As I understand it (Hector- please correct me if I get anything wrong), the trial that Hector participated in had him taking Sofosbuvir + Ribavirin for 48 weeks. He was undetected from week 4 on.  Unfortunately, he was not able to get a liver transplant during that period and treatment ended at 48 weeks. A month later, he had a viral breakthrough before transplant. After he was transplanted, the new liver was infected with the virus.

The question I believe the trial wanted to answer is would a patient who is undetected for the virus during this 48 week treatment, avoid being infected with the virus if he/she is transplanted during the 48 week treatment period while he/she is undetected for the virus.

I don't know if they have any data on that question.

Hector - if you read this post, can you comment?

Nan

[pooh55811]

The one trial I did find using Sofosbuvir and Ribavirin for 12 weeks was the Electron trial. This trial did not include Cirrhotics.

http://www.natap.org/2013/EASL/EASL_30.htm

In Genotype 1 treatment naive patients without Cirrhosis the SVR12 rate was 84%. However, in previous null responders, the SVR12 rate was only 10%.

I know that does not give you an answer about people who might treat for 24 weeks or longer.

[pooh55811]

I recall reading the statistics from the studies. I will try to find them. Hector will know the answer to that question, though.

[Upbeat]

Thanks
I understand the pre and post transplant FDA apprroval.  The thing is I am trying at all costs to avoid a transplant.  To that end I have had RFA to the Tumor and if I can kill the virus I hope that the liver will heal just enough to stop any new tumors from growing.  I know its a long shot  The question is Will this treatment actually create SVR or is it only going to help the virus to not infect a new liver?  I am  not sure anyone can answer that

[pooh55811]

Actually, I see Hector posted in your other thread.

To quote part of Hector's post:

""SOVALDI in combination with ribavirin is recommended for up to 48 weeks or until the time of liver transplantation, whichever occurs first, to prevent post-transplant HCV reinfection [See Use in Specific Populations (8.9)]."
"8.9 Patients with Hepatocellular Carcinoma Awaiting Liver Transplantation" "

"NOTE: This trial's primary objective was to study if Sovaldi + ribavirin could prevent recurrence of hep C post transplant not to see who could be cured before transplant. It was the results from this study that got approval  for the use of Sovaldi + ribavirin in patients with hep C and HCC. For efficacy and safety. All 61 of us were expected to be transplanted within one year. In other words we would all be treating when we had our transplants. For me I didn't get a transplant during the 48 weeks of treatment and Gilead wouldn't let me treat longer so I relapsed and now have hep C after my transplant."

http://www.medhelp.org/posts/Hepatitis-C/sovaldi-and-ribavirin-results-after-17-days/show/2107099#post_10001521

[pooh55811]

If I recall correctly, Hector was on Sovaldi and Ribavirin for 48 weeks. Then he had to stop. They would go only 48 week with the Sovaldi and Ribavirin. The virus became Detectable again after he stopped the Sovaldi and Ribavirin and before he could get his transplant. But he did finally get his transplant.  

I am sure he will know the answers to any questions you have about your situation.

[pooh55811]

I looked at your profile. You have Cirrhosis and had HCC. It appears you are waiting for a transplant. If that is the case, they want to keep you Undetectable until you get a transplant.  If you stay Undetectable until you have the transplant most likely your new liver will not become infected with HCV. The way to keep you Undetectable is to keep you on treatment until you get the transplant.

Hector knows all about this. He was in the same or a similar situation as you are. He will probably respond to your post, but if he does not, you may want to send him a PM and ask him any questions that you have.

Best of luck.