gen 3 sof/rib relapse

[TIMBOY67]

just relapsed 4 week eot after 16 week arm of sof/rib trial , ideally 24 week arm would have prob had better chance of svr
but had to accept what i was randomised to , still really gutted , thought i had a solution this time , hopefully some other treatment will suit in future ..any advise welcome


GEN 3 , PREV NON RESPONDER SOC INT/RIB 2012 , NON CIRROTIC , 16 weeks sof/rib

[Type0]

I am Gen 3 treatment-naïve, and I try to keep my eye on the new treatments for Gen 3. The only promising option is daclatasvir (an HCV NS5A replication complex inhibitor) plus sofosbuvir (a nucleotide analogue HCV NS5B polymerase inhibitor). "A total of 92% of 26 patients with genotype 2 infection and 89% of 18 patients with genotype 3 infection had a sustained virologic response at wee k 12. ". We have to be cautious regarding the results report ed for HCV genotype 3, the SVR rate was of 89% after 24 weeks of daclatasvir plus sofosbuvir. This SVR appears to be similar to SVR obtained with sofosbuvir plus ribavirin given during 24 weeks in genotype 3 non-cirrhotic patients http://hepatitiscnewdrugs.blogspot.com/

Another treatment is Sovaldi/GS-5816

Study GS-US-342-0102 (Oral #111), is an ongoing randomized Phase 2 clinical trial in which treatment-naïve, non-cirrhotic patients with genotypes 1-6 HCV infection received a 12-week course of SOF plus the pan-genotypic NS5A inhibitor GS-5816. Patients received SOF 400 mg and either GS-5816 25 mg (n=77) or GS-5816 100 mg (n=77). In this study, 94.8 percent (n=73/77) of patients receiving the 25 mg dose of GS-5816 and 96.1 percent (n=74/77) of patients receiving the 100 mg dose achieved SVR12.
http://hepatitiscnewdrugs.blogspot.com/2014/04/easl-gilead-announces-phase-2-results.html
There is concern about Sovaldi and virus mutation. But it sounds like Sovaldi holding up with no viral break through. May be you can still use it. If not- anything with "buvir" ending supposed to be pan-genotypal.  

[HectorSF]

I am very sorry to hear that you failed your treatment. As you know genotype 3 treatment experienced patients are now the most difficult patients to treat.

You are correct trial data shows that 24 weeks of SOV + Riba is the optimal treatment.

The American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA )recommended treatment is 24 weeks if not using interferon which ups the SVR rate from 63% (in FUSION study) with 16 weeks of treatment to 87% in those without cirrhosis (VALANCE study) with 24 weeks of treatment.

Here are the current recommended treatments for HCV genotype 3 PEG/RBV nonresponders.
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Recommended regimen for HCV genotype 3 PEG/RBV nonresponders.
Daily sofosbuvir (400 mg) and weight-based RBV (1000 mg [75 kg]) for 24 weeks is recommended for retreatment of HCV genotype 3 infection.

or

Alternate regimen for HCV genotype 3 PEG/RBV nonresponder patients who are eligible to receive IFN.
Retreatment with daily sofosbuvir (400 mg) and weight-based RBV (1000 mg [75 kg]) plus weekly PEG for 12 weeks is an alternative for IFN-eligible persons with HCV genotype 3 infection.
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The phase 3 FUSION trial compared 12 weeks (n=103) with 16 weeks (n=98) of daily sofosbuvir (400 mg) and weight-based RBV (1000 mg to 1200 mg) in genotype 2 or 3 HCV-infected patients in whom previous PEG/RBV therapy had failed. Of patients, 63% had genotype 3; 34% of all patients had cirrhosis. Because persons who had experienced prior relapses to IFN-based therapy accounted for 75% of patients, the number of patients with a prior nonresponse in the study was limited. The SVR rate for genotype 3 patients in the 12-week arm was 30% (19% among patients with cirrhosis and 37% among those without cirrhosis). Extending therapy to 16 weeks increased the SVR rate among genotype 3 patients to 62% (61% among patients with and 63% in those without cirrhosis).

Based on results from FUSION, the phase 3 multicenter, randomized placebo-controlled VALENCE trial was amended to evaluate the effect of extending sofosbuvir plus RBV therapy to 24 weeks in all patients with HCV genotype 3. As with the FUSION study, most (65%) treatment-experienced patients had relapsed. The SVR12 rates after 24 weeks of therapy for treatment-experienced patients with genotype 3 was 79% (60% among patients with and 87% in those without cirrhosis). The increased efficacy with 24 weeks of sofosbuvir plus RBV therapy across all fibrosis stages combined with a favorable safety and tolerability profile supports the recommendation to use 24 weeks of sofosbuvir plus RBV in all genotype 3 patients despite the minimal number of patients studied to date. The response rate for HCV genotype 3-infected patients with cirrhosis treated for 24 weeks in the VALENCE trial (60%) was similar to that observed after 16 weeks of treatment in the FUSION trial (61%). Although longer treatment duration with a well-tolerated regimen may potentially be more successful in these more difficult-to-treat patients, data remain limited. Either duration of treatment is considered acceptable at this time

As you know doing trials are a risk as there is no guarantee of success. You can feel good that you have helped others and maybe yourself to know that 24 weeks of SOV + Riba treatment is the optimal treatment for genotype 3 previous nonresponders.

I also failed Sovaldi treatment (48 weeks of SOV + RIBA) but now patients with liver cancer awaiting liver transplant have a FDA approved hep C treatment which can prevent them from infecting their new donor liver with the virus. For that I am grateful.

New and better treatments are going soon!

Be well.
Hector

[pooh55811]

I am very sorry you relapsed. I know it is devastating. However, new treatments are in the pipeline so hang in there and something will come along that will cure you.

Yes, 24 weeks of treatment had much higher success rates (SVR). I am surprised they treated you for only 16 weeks. The data showing that 24 weeks of treatment has much higher SVR rates  has been known for several months. Not sure why they would still be treating GenoType 3 for only 16 weeks when all of this is common knowledge.

It looks like you were in a trial (since you were randomized to get 16 weeks). If you have insurance and can afford to see a Hepatologist, that would probably be advisable. A Hepatologist should know which treatments will be available and when and also know which will be best for you.

In the meantime, try to hang in there as something will come along for you in the future. Best of luck.