Type 2 Hep C Recurrence 8 weeks post-Solvaldi + Ribovarin Treatment

[solott55]

This question is for Ipoterm in particular but would be grateful for any input:

My father has Type 2 Hep C - almost 20 years ago he received a liver transplant and over 10 years ago he was able to wean himself off of anti-rejection drugs and has been living medication-free since so a bit of a special case. About 7 years ago he attempted the Ribavirin + Peginterferon treatment unsuccessfully. In the Fall of 2014 he was approved to receive free treatment of Solvaldi + Ribavirin for 24 weeks (gradually ramping up the Ribavirin dosage to make sure he could handle it).  His viral load dropped rapidly and he finished the treatment in February with virus undetected.  It was still undetected 4 weeks later.  Sadly at the 8-week mark it had reappeared (he already suspected it based on how he was feeling).  He was under the impression that there was a second treatment option available but found out last week that because of his type there were no further options at this point - as usual his specialist was busy and it was a quick call and he was not clear as to whether there might be something else to try further down the road. Just hoping to hear some hopeful/encouraging words I can pass along to him that he doesn't have to resign himself to living with the disease forever just yet - do you (or anyone) know of any other options available now or things coming down the pipe?  Many thanks!

[lporterrn]

Hi,
First, just my sympathy. That is a long time to be on ribavirin, and hard to hear that it didn't pay off.

He heard right, there aren't other options for him at this moment. However, I do have encouraging words:
1) Despite the lack of sustained response, he very likely got some improvement in liver disease, and bought himself some time.
2) Studies using BMS's daclatasvir with Gilead's sofosbuvir look promising.  This is a much easier regimen to take. Here's some info: http://www.nejm.org/doi/full/10.1056/NEJMoa1306218 BMS resubmitted an application to the FDA on March 12, 2015 for daclatasvir in combination with sofosbuvir (Sovaldi) for hepatitis C genotype 3. If approved, his doc can prescribe it, and it wouldn't surprise me if the HCV guidelines (http://www.hcvguidelines.org/full-report/retreatment-persons-whom-prior-therapy-has-failed add it in.

Hope this helps...

[solott55]

Thank you so much - it's been a long, interesting but often hard road - for all of us but especially my father of course.  If you don't mind I have a couple of follow-up questions:

1) Re declatasvir + sofosbuvir - my father is genotype 2 and you mentioned this has been submitted for genotype 3 - are you saying it could possibly be used for type 2 as well?

2) In the link you provided I noted an alternative regimen of sofosbuvir + ribovarin + interferon - is it possible they could try that at some point in the future or once you've relapsed after a sofosbuvir treatment that's no longer an option? I thought I read elsewhere that the HCV doesn't build a resistance to the sofosbuvir but could be mistaken.

Again thank you very much for your kind words and info!

[lporterrn]

1) Yes, the daclatasvir studies for GT 2 look quite good.
2) You bring up a good point, but the data are limited. First, the retreatment studies seem to be with pts who failed PEG/RBV. Second, the #'s are small. Third, the HCV Guidelines don't make specific recommendations for retreating GT 2 DAA failures. (I do think we'll see them soon - 2 more liver-related meetings this year)

Here's some info - it is from: http://www.hepatitisc.uw.edu/page/treatment/clinical-trials/52

LONESTAR-2: In the phase 2 LONESTAR-2 trial, treatment-experienced patients with genotype 2 or 3 infection received open-label sofosbuvir plus peginterferon plus ribavirin for 12 weeks. Among the treatment-experienced patients with genotype 2 infection, 22 (96%) of 23 achieved an SVR12. Of note, more than 50% of the patients in this study had cirrhosis and 13 (93%) of 14 patients with genotype 2 infection and cirrhosis obtained an SVR12.

Genotype 2: Future Treatment Options
Future Treatment Options for Patients with HCV Genotype 2: Moving forward, it is highly likely that use of peginterferon for genotype 2 infection will completely phase out. Relatively few studies are ongoing to examine future therapies for genotype 2, primarily because the extremely high SVR rates observed with a 12-week course of the all-oral regimen of sofosbuvir and ribavirin has generated a standard of success that will be very difficult to exceed, or even match. Future studies could potentially look at shorter-course (6 to 8 weeks), but would need to show an SVR rate of at least 95% to serve as an attractive alternative to sofosbuvir pus ribavirin.
Daclatasvir plus Sofosbuvir: This investigational pangenotypic NS5A replication
complex inhibitor is currently in phase 3 trials. In study AI444-040, a phase 2 trial involving patients with genotypes 1, 2, and 3, a 24-week course of daclatasvir 60 mg once daily plus sofosbuvir 400 mg once-daily, with or without ribavirin, produced SVR rates of 86% to 93% in patients with genotype 2 or 3, and was well-tolerated and safe. Additional phase 2 trials with daclatasvir in combination with sofosbuvir are ongoing. Daclatasvir for 12 weeks combined with peginterferon lambda and ribavirin for 12 or 24 weeks is under study in a phase 3 trial for patients with genotype 2 or 3 infection.

That said, they do use PEG+RBV+Sovaldi in Europe - the trick is trying to get it covered in the U.S. - It would be off-label, and without solid recommendations in the US literature, it may be hard to win approval. Here are the EASL recommendations: http://www.easl.eu/research/our-contributions/clinical-practice-guidelines/detail/recommendations-on-treatment-of-hepatitis-c-2015/report/4

[smaugslugger]

I have type 2 and am on sovaldi/ribo. I saw my doc yesterday and asked her "what if it doesn't work?" She echoed what Lucinda said----that the treatment basically knocks the wind out of the virus if it doesn't cure it and that liver function will be better. She also said that in a year another treatment will be available for type 2, and that it will be used as a backup. I didn't get the impression that failing treatment meant it was a done deal.

[solott55]

Thank you mmolinde (and thanks again to Iporterrn above) - great to hear that confirmation - best of luck to you with your treatment!