Wow Mallani:

I didn't know you achieved SVR. Gongrats!!

I finished my 12 weeks of the Gilead combo. Have been undetected but, I am cautious and hopeful.

Hi Garfield,

Thanks for the link you provided. As usual, I have a few comments.

I agree that too many trials exclude cirrhotics. This is particularly true of the Gilead trials. As time goes on, we will have more cirrhotics seeking Rx, and choice of Rx will be 'toss a coin in the air'.

I do not understand why trials with poor results for cirrhotics do not extend Rx time longer. Why is 24 weeks the end point?  Would 36 weeks or 48 weeks give better results?

There are too many drugs in the pipeline. It has been shown that NS-5B nucleotide analogues are by far, the most resistant to RAV's. It seems obvious that a NS-5B nucleotide analolog antipolymerase plus a NS-5A blocker are the best combination, so why are we persisting with even more antiproteases. Many trials do not even include an NS-5B blocker.

Much is made of the RAV resistance of Sofosbuvir. In the Phase 1 Trial with about 20 patients using Sofosbuvir as monotherapy, all patients relapsed due to the S282T mutation. The Fusion Trial with Sofosbuvir/ Riba for 12 weeks was also disappointing, with only 50% of patients achieving SVR. Sofosbuvir is obviously a great drug, but needs to be used with another suitable DAA for a suitable period of time.

The article gave a link to how low and middle income countries were now able to treat HCV. This is great, but it essentially means such countries can now afford Peg.- big deal! At least it's a start.

http://www.pipelinereport.org/2013/hcv-global-access

Hello Do

Its a beautiful thing that your helping your friend with her problem, its show great compassion on your part.

As I am well aware of her type of situation the best advice for her is to be patient as the newer treatments come available. In the meantime show her how to eat a healthy diet for a person with liver advanced disease. 

Do keep up your helpful good deeds.

Matt

Thanks Jill, Garfield !

Garfield : BMS has asked her to follow her for 3 years.  They will probably identify the RAVs and I hope they will let her know.

It's really hard when you have been a cirrhotic for so long to be told you, once more, will have to wait.

The last Trial took must of her hair off, all that for nothing.

At least she has been able to hope to be cured.

Thanks a lot for the help, I do appreciate.

Do

Hi Do,

         Daclastavir is a NS5A-Inhibitor like abt-267, Asunaprevir is a Protease Inhibitor like abt-450.

It could be, she has mutations in both groups. Gilead is the only one  for her with Sofosbuvir as a nucleotide polymerase inhibitor

but Ledispavir is also a NS5a-Inhibitor. Perhaps Miravirsen will be the next star in hcv therapy as  mRNA-targeting.

In a study there isn't the possibility to compose the drugs. When I asked the " chief-doc" what, when I would  relapse with abbvie,

his answer was, waiting, identifying RAVs, composing drugs. It must be feared that at the moment she can only care her liver.

a very good outline:    http://www.pipelinereport.org/2013/hcv    

lots of love

Hi again, Do, yes it`s unfortunate that your friend was put on the BMS trial, although with such high success rates she was very unlucky to have relapsed.  Malcolm has a good point that she could possibly be excluded from another treatment using a NS5A inhibitor, for example Ledipasvir, so I`m not sure at this point what exactly her future options will be.

It`s good to hear that she is so active and busy in her life anyway, and she is still relatively young compared to a lot of us here.  It is sad though, and I hope a suitable therapy becomes available for her at some point.

Hi Jill, Malcom,

Thanks a lot for your answer.

Her trial doc told her she is the only one to have fell in her hospital. She is a very active, 48 years old teatcher, she has never stoped working during any of her treatments, she has a strong mind.

I will tell her about your answer next Friday when she comes to my place. I feel so sad for her. I beleive she should have been put on Gilead instead of BMS, I do not know why her doc has choosen BMS, we are in the same hôpital, but different doct, mine gave me AbbVie, but the hospital do have Gilead trial too. Bad choice.

About ultrasounds, cirrhotic patients get ultrasounds every 3 month here in Paris, isn't that enough Malcom ? about biopsie : many French doctors want biopsies, as many do not ... But she would say yes if necessary any way. Scanner said her liver had normal size.

Do

Hi Do,

Your friend is extremely unlucky. I presume she had 24 weeks of quad therapy. Geno 1a doesn't do as well as 1b, but I enclose a link to some BMS quad trial results.

http://news.bms.com/press-release/rd-news/investigational-hepatitis-c-quad-therapy-regimen-daclatasvir-and-asunaprevir-p

She now has very limited options. As Jill said, she is unable to have any further antiproteases at this point in time, and she may be barred from having any NS5A inhibitors.  The question of whether patients can be retreated with the same site blocker still needs to be resolved.  The prevalence and duration of resistant mutations has everyone confused.  As she is cirrhotic, she needs 6 monthly Ultrasounds to exclude HCC, and a further liver biopsy would be very useful (although you hate them in France!).

Hi Do, I can understand that you friend is very keen to get onto another trial after her unsuccessful experiences so far, and especially as she has been diagnosed with cirrhosis.  An ultrasound won`t really show a true picture of liver damage, a biopsy gives a much more accurate result.

It sounds like your friend has done a BMS `Quad` trial with includes Asunaprevir, a Protease Inhibitor, which means she won`t  be accepted for any other trial which also includes a PI, so that rules out the Abbvie trials.  I think her best bet would be to try and get onto a trial of Gilead`s Sofosbuvir plus Ledipasvir if possible, if there are any suitable ones coming up in France in the near future.

Hope that helps, good luck to her. 

Hi all,

My friend would need some advice from all of you to tell her what could be the best Trial for her.

First she lives in France. She had a blood transfusion 30 years ago and she is GENO 1a, A3/F4 (cirrhosis). She had had 3 treatments, all with interferon. She did not answer at all for the first 2, then started a new trial last August with BMS : 650032/BMS 790052. ( Daclastavir, Asunaprevir) Riba and Interferon.

For the first time, she became negative at week 4 till the last week 24 (end of treatment) when she was positive again (January 2013).

Her doc does not propose her any trial, just gives her vitamine E. He seems to beleive her body refuses Interferon.

She is desesperate to start a new trial. Ultrasound from last week says her liver is ok.

Any idea ?

Thanks a lot,

Do