Starting Sovaldi - Prior relapser

[48weeks]

Just got a call from my hepatologist's office to start the process of getting me started on Sovaldi.  I am a gt 1a, twice non-responder to Int+Rib and I relapsed after 48 weeks of triple therapy with Incivek. Anyone know what the cure rate for this treatment is for a relapser?

[MagTX]

Hi, I can try and help to find an answer.

What will your protocol be, which meds and for how long will you do this tx?

[48weeks]

That would be great. I just can't find anything specific. When I went on Incivek I did so thinking the cure rate was 80+ percent, but found out all along my chances were really only 30 percent. I am a genotype 1a, I relapsed from triple therapy with Incivek after 48 weeks. Not sure what my liver status is right now, getting a biopsy in January. Thanks for anything you can find.

[48weeks]

I meant to add that in the 90's I was a non-responder to two Int+Rib treatments

[MagTX]

I think we will need more info on your exact protocol your hep doc is planning to use before finding such results from previous trials, etc..
I asked a couple questions up above :)

[48weeks]

The meds are the new Sovaldi which is Sofusbufir+Interferon+Ribivirin supposedly for 12 weeks.

[MagTX]

Thank you!  That will help facilitate some answers for you :)

[MagTX]

It is estimated that the response rate in patients who previously failed pegylated interferon and ribavirin therapy will approximate the observed response rate in NEUTRINO subjects with multiple baseline factors traditionally associated with a lower response to interferon-based treatment (Table 9). The SVR rate in the NEUTRINO trial.

http://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/sovaldi/sovaldi_pi.pdf

[can-do-man]

Not sure your doctors reason as it seems clear interferon does not work for you. Though I do wish you the best.

HCV Genotype 1

The ELECTRON team then proceeded to test sofosbuvir in people with more difficult-to-treat HCV genotype 1, both treatment-naive and null responders to previous interferon-based therapy. They looked first at the same combination of 400 mg sofosbuvir once-daily plus 1000-1200 mg ribavirin for 12 weeks.

As Gane reported at this year's Retrovirus conference, although all participants saw a rapid decline in HCV RNA and had undetectable viral load at the end of the 12-week course of treatment, almost all genotype 1 prior null responders relapsed soon thereafter, resulting in a very low cure rate.

Given that sofosbuvir plus ribavirin as a dual regimen is not adequate for this more difficult-to-treat patient population, researchers then asked whether adding a second direct-acting agent could increase cure rates.

http://www.hivandhepatitis.com/hepatitis-c/hepatitis-c-topics/hcv-treatment/3860-aasld-2012-sofosbuvirgs-5885ribavirin-shows-high-early-response-rates-for-genotype-1-hcv

[willbb]

Having the same result with an INF based therapy 3 times and once with a protease added(Incivek)  I also wonder what your physician's logic is.

Have you discussed with him/her possibly waiting until the virus can be attacked  from multiple fronts (ie two or more of the all oral drugs) and leave the failed INf out of the mix?

best of luck..
Will

[MagTX]

I agree can-do.  Seems the 3 DAA's are working the best for the geno 1's null responders and for those who previously relapsed.

[willbb]

Also Has the physician had any discussion with you about possible resistance issues developing .....meaning if you failed the NS3 /4 drug ( Incivek)  because  partially of the insensitivity to INF. and you happen to fail the NS5B  drug (sovaldi) for the same reason then your options may be very limited beyond that  as resistance issues are still greatly unknown.

Best...
Will

[48weeks]

Thanks Magtx, I wonder if my Hepatologist knows what he's doing. He's Mr. Big at Einstein in Philly. Everything everyone is saying makes sense, wonder what he's thinking.

[MagTX]

You're welcome.
I think I would get a second opinion on re treating again with the inf and RIBA. You may very well have a good hep doc, but going thru tx again after a few failed attempts can cause resistance issues like the other posters have said, and you want the best chance at beating this as possible with solid knowledgable advise given before hand.
I'm a geno 1a relapser ( did 48 weeks of SOC) and approaching my next chance at beating this virus very cautiously!
Good luck and please let us know what you decide.

[can-do-man]

Have you read through this thread? This is something I would bring up to my doctor if treatment is needed ASAP.

http://www.medhelp.org/posts/Hepatitis-C/Anyone-know-if-Insurance-will-pay-for-these-new-drugs/show/2058000

[48weeks]

Looks like I have my answer according to p.21 of the Sovaldi package insert. I would be looking at a cure rate of probably 71% which is significantly better than the 30% I was looking at for Incivek, but much lower than the COSMOS study with Simeprevir+Sofusbuvir+Ribivirun. which is over 90%. I wonder if I would be able to talk my Hepatologist into going off label. I wonder what the approach would be. Do they have a criteria that must be met to go off label. Would the Dr. be liable for anything with that process? Here is the info from p.21

It is estimated that the response rate in patients who previously failed pegylated
interferon and ribavirin therapy will approximate the observed response rate in
NEUTRINO subjects with multiple baseline factors traditionally associated with a lower
response to interferon-based treatment (Table 9). The SVR rate in the NEUTRINO trialin genotype 1 subjects with IL28B non-C/C alleles, HCV RNA >800,000 IU/mL and
Metavir F3/F4 fibrosis was 71% (37/52).



I don't know what my Metavir score is or my IL28B is but it looks like if I don't have Cirrhosis my worse case scenario is a 71% cure rate.

[purplecat]

I agree with can-do-man. Are you advanced stage fibrosis, is this why treatment might be needed ASAP?  Non-responder and interferon?  what is your IL28B?.  Have you  had this tested?  Is the IL28B a factor since interferon is part of the treatment? It's not a factor with Sovaldi when used with the GS5885, but what about Interferon?  I would want all these answers from my Hepatologist.  The second half to the Sovaldi(sofosbuvir) will be out next year.  Can you wait?
Do all your homework and approach this 4th try with caution.  Best Wishes.

[48weeks]

I see you are also a gen 1a relapser. I stumbled across the 135 posts associated with OC and 3xlucky's experience with Sovaldi, and they seem to be having some serious success and they are also both treatment experienced. While I have asked my Hepatologist to look into going off label with Simeprevir+Sofosbrevir, after rereading their experiences, I may be excited again about Sovaldi.  Thoughts?

[MagTX]

Hi 48,  there's not that much data out there that I can easily find on relapsers that have previously TX'd with a protease inhibitor ( Incivek or Boceprevir),  did triple therapy, and then treated with Sovaldi, a polymerase inhibitor along with the other DAA's. I think there have been some trails with others in your exact situation that got into Gilead's trials with Sovaldi, but I'm not as well informed on this scenario since I haven't ever TX'd with a protease inhibitor. Perhaps there will be new info coming around soon as the population who failed triple therapy may soon be treating with Sovaldi and semeprivir, off label, if that is even a choice for this group...it would be a good idea to discuss what options you have with a sharp hep doc, and ask about the possible mutations if any the protease inhibitor may have caused with the virus during and after your relapse. Remember semeprivir is also a protease inhibitor, so these are some of the questions I would ask someone who's "very" experienced, about taking your next step.
My advise is that if you don't have to rush in to this, and your hep doc says you can wait a while, then I would. Or, look at trial data, discuss with your doc and go from there. ;)

[JimmyMose]

If you are using insurance to pay for the drugs you need to find out what they will cover. Also what the  U.S. Patient Assistance Program might cover  Off label might be a big problem.

[Upbeat]

Talked to my doctor today and was told its going to be awhile before the ins and pricing is worked out.

[can-do-man]

One thing I am curious about is when approval was sought it stated quite clearly for genotype 1 that was treatment naïve and as far as I know that has not changed so wouldn't that be considered going off label if one has treated prior?

[copyman]

Get a 2nd opinion from Dr Reddy at Univ of Penn.

Problem with new drug Sovaldi is that insurance companies aren't going to pay the $84,000 for 12 week treatment. Gilead will have to lower price or their drug will never take off. There is talk of patent infringement and other things going on behind the scenes. No one knows what is going to happen with court battles, etc.

Insiders must know something because Gilead Sciences stock is sinking fast.

Best of luck

[Groovy777]

Gild is off 5%...?..That's it, Haven't you heard sell the News?
Everyone new it was going to get approved..That was the run up..
Gild is a Buy and Sovaldi with 5816 is a Cure
Copy

[hepcat1954]

1) IL28B is an indicator of how one might respond to Interferon.  There's no known correlation between IL28B and response to Direct Acting Antivirals (DAA's).

2) Sofosbuvir (Sovaldi) is a RNA polymerase inhibitor, not a protease inhibitor, so your resistance to protease inhibitors (which you undoubtedly have) on this drug is a non-issue.

3) Sofosbuvir, with NS5A inhibitors (Daclatasvir or Ledipasvir - both nucleotide analogue inhibitors), has shown SVR rates of up to 100% in people infected with HCV.  

4) If your insurance company does pay for off-label, the fastest, for-sure way to cure your HCV is to take (off-label) Sofosbuvir with either Dataclatasvir or Ledispasvir, whichever gets approved first.

I'm 1a and also failed triple (first tx attempt) in November of 2011 (Incivek/Riba/Interferon) after 12 painful weeks.  However, in 2013 I got on a 12 week Gilead all-oral Sofosbuvir + Ledipasvir study and was UND in 14 days and I achieved SVR24 in July 2013.  Unlike triple, it was quick, effective, so easy and no sides!  In my case I took one pill/day but if you're doing it off-label, you'd be taking 2 pills/day.

Good luck to you!

HC